Wise as serpents, &c. It is a proverbial way of speaking; and an admonition to be circumspect and discreet, but harmless, innocent, sincere in all our actions and dealings. (Witham)

Simple. That is, harmless, plain, sincere, and without guile. (Challoner)

In the midst of wolves. Although Christ sent his apostles not only against wolves, but even into the very midst of wolves, still he commands them to behave with the meekness of sheep, and simplicity of doves. Thus he evinces the greatness of his power, in overcoming the wolves by the sheep, which were continually exposed to be devoured and torn in pieces by them, still never failing to change the fierce nature of the ravenous wolf into their own nature, in mildness and innocence. As long as we retain the nature of sheep, we easily overcome our adversaries; but no sooner are we changed into wolves, than we become the derision of our enemies: the supreme Pastor, who superintends the sheep, not the wolves, withdrawing from us the powerful protection of his grace, and leaving us to the misery of our own weakness.

Our Saviour, in his infinite wisdom, knew full well the nature of things; passion was not to be overcome by passion, but by meekness only. Thus the apostles did, when the Jews having apprehended them, said, Have we not again and again commanded you not to teach in this name? (Acts, Chap. iv.) Though they had the power of working the greatest miracles, yet they let nothing harsh, nothing severe, escape them, either in words or actions. With simplicity they made answer, Judge ye, if it be just to hear you rather than God; and at the same time shewed their prudence, saying, We cannot but speak what we have heard and seen. (St. Chrysostom, hom. xxxiv.)

As sheep, &c. He compares them to sheep, not only because of their innocence, but also because they were sent unarmed and destitute of all human support. (Menochius)

Wise, &c. That you may guard against the snares of your enemies. The prudence of the serpent is celebrated, because when it cannot escape, it strives at least to preserve its head free from hurt, whilst it leaves the rest of its body exposed. Thus Christians, who have Christ for their head, must preserve his faith and religion, though with the loss of every thing else. (Menochius)