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Matthew 10:16

I am sending you out like sheep among wolves. Therefore be as shrewd as snakes and as innocent as doves.
David Brown
To be left exposed, as sheep to wolves, would have been startling enough; but that the sheep should be sent among the wolves would sound strange indeed. No wonder this announcement begins with the exclamation, Behold.
Be ye therefore wise, etc Wonderful combination this! Alone, the wisdom of the serpent is mere cunning, ... the harmlessness of the dove little better than weakness ... in combination, the wisdom of the serpent would save them from unnecessary exposure to danger; the harmlessness of the dove, from sinful expedients to escape it. In the apostolic age ... how harmoniously were these qualities displayed! Instead of the fanatical thirst for martyrdom ... there was a manly combination of unflinching zeal and calm discretion, before which nothing was able to stand.

Matthew Henry
... what may a flock of poor, helpless, unguarded sheep expect, in the midst of ... ravenous wolves, but to be worried and torn?
Note, Wicked men are like wolves, in whose nature it is to devour and destroy. God's people, and especially his ministers, are like sheep among them, of a contrary nature and disposition, exposed to them, and commonly an easy prey to them. It looked unkind in Christ to expose them to so much danger, who had left all to follow him; but he knew that the glory reserved for his sheep, ... would be a recompense sufficient for sufferings as well as services. They are as sheep among wolves, that is frightful; but Christ sends them forth, that is comfortable; for he that sends them forth will protect them and bear them out. But that they might know the worst, he tells them ... what they must expect.
Be ye wise, etc ... a precept, recommending to us that wisdom of the prudent, which is to understand his way, as useful at all times, but especially in suffering times. “Therefore, because you are exposed, as sheep among wolves; be ye wise as serpents; not ... foxes, whose cunning is to deceive others; but ... serpents, whose policy is only to defend themselves and to shift for their own safety.” ... disciples of Christ are hated and persecuted as serpents ... their ruin is sought ... they need the serpent's wisdom.
Note, It is the will of Christ that his people and ministers, being so much exposed to troubles in this world, as they usually are, should not needlessly expose themselves, but use all fair and lawful means for their own preservation. .... We must be wise, not to pull trouble upon our own heads; wise to keep silence in an evil time and not to give offence, if we can help it.
Be ye harmless, etc “Be mild ... meek ... dispassionate; not only do nobody any hurt, but bear nobody any ill will; be without gall, as doves ... this must always go along with the former.” They are sent forth among wolves, therefore must be as wise as serpents, but they are sent forth as sheep, therefore must be harmless as doves. We must be wise, not to wrong ourselves, but rather so than wrong anyone else; must use the harmlessness of the dove to bear twenty injuries, rather than the subtlety of the serpent to offer or to return one.
Note, It must be the continual care of all Christ's disciples, to be innocent and inoffensive in word and deed, especially in consideration of the enemies they are in the midst of. We have need of a dove-like spirit, when ... beset with birds of prey, that we may neither provoke ... nor be provoked ....

Albert Barnes
... That is, I send you, inoffensive and harmless, into a cold, unfriendly and cruel world. Your innocence will not be a protection.
... Serpents have always been an emblem of wisdom and cunning, Gen 3:1. The Egyptians used the serpent in their hieroglyphics as a symbol of wisdom. Probably the thing in which Christ directed his followers to imitate the serpent was in its caution in avoiding danger. No animal equals them in ... rapidity and skill ... in escaping danger. So said Christ to his disciples, You need caution and wisdom in the midst of a world that will seek your lives. He directs them, also, to be harmless, not to provoke danger ... do injury, and ... make their fellow-men justly enraged against them.
Doves are ... a striking emblem of innocence. Most people would foolishly destroy a serpent, be it ever so harmless, yet few are so hard-hearted as to kill a dove.

Marvin Vincent
I send, etc (ego apostello) Cognate to the word apostolos (apostle). The I is emphatic: “It is I that send you forth.”
Wise (phronimoi) So AV and RV. Denoting prudence with regard to their own safety. Wycliffe, "wary".
Harmless (akeraioi) Lit, unmixed, unadulterated. Used of wine without water, and of metal without alloy. Hence guileless ... Luther, "without falsity". Cf Rom 16:19; Phi 2:15. They were to imitate the serpent's wariness, but not his wiliness. “The presence of the wolves demands that ye be wary; the fact that ye are my apostles (compare “I send you”) demands that ye be guileless” (Dr Morison).