Genesis 3:15

And I will put enmity between thee and the woman
Between whom there had been so much familiarity, not only while they had the preceding discourse together, but before; for it is conjectured by some ^F25, that she took a particular liking to that creature, and was delighted with it, and laid it perhaps in her bosom, adorned her neck with its windings, or made it a bracelet for her arms; and being a peculiar favourite, the devil made choice of it as his instrument to deceive her; but now being beguiled hereby, she conceived an antipathy against it, and which is become natural between the serpent and man; man abhors the sight of a serpent, and the serpent the sight of man; and the spittle of a man and the gall of a serpent are poison to each other; and this antipathy is observed to be stronger in the female sex: and this was not only true of the particular serpent that deceived Eve, and of the particular woman, Eve, deceived by him, but of every serpent and of every woman in successive ages; and is also true of Satan and the church of God in all ages, between whom there is an implacable and an irreconcilable hatred, and a perpetual war:

and between thy seed and her seed;
the posterity of Eve, mankind, and the production of serpents, between whom the antipathy still continues, and mystically the evil angels and also wicked men called serpents; and a generation of vipers on the one hand, and the people of God on the other, the seed of the church; the latter of which are hated and persecuted by the former, and so it has been ever since this affair happened: and especially by the seed of the woman may be meant the Messiah; the word "seed" sometimes signifying a single person, ( Genesis 4:25 ) ( 15:3 ) ( 21:13 ) and particularly Christ, ( Galatians 3:16 ) and he may with great propriety be so called, because he was made of a woman and not begotten by man; and who assumed not an human person, but an human nature, which is called the "holy thing", and the "seed of Abraham", as here the "seed of the woman", as well as it expresses the truth of his incarnation and the reality of his being man; and who as he has been implacably hated by Satan and his angels, and by wicked men, so he has opposed himself to all them that hate and persecute his people:

it shall bruise thy head;
the head of a serpent creeping on the ground is easily crushed and bruised, of which it is sensible, and therefore it is careful to hide and cover it. In the mystical sense, "it", or "he, Hu", which is one of the names of God, ( Psalms 102:27 ) ( Isaiah 48:12 ) and here of the Messiah, the eminent seed of the woman, should bruise the head of the old serpent the devil, that is, destroy him and all his principalities and powers, break and confound all his schemes, and ruin all his works, crush his whole empire, strip him of his authority and sovereignty, and particularly of his power over death, and his tyranny over the bodies and souls of men; all which was done by Christ, when he became incarnate and suffered and died, ( Hebrews 2:14 Hebrews 2:15 ) ( Colossians 2:15 ) ( 1 John 3:8 )

And thou shall bruise his heel;
the heel of a man being what the serpent can most easily come at, as at the heels of horses which it bites, ( Genesis 49:17 ) and which agrees with that insidious creature, as Aristotle ^F26 describes it: this, as it refers to the devil, may relate to the persecutions of the members of Christ on earth, instigated by Satan, or to some slight trouble he should receive from him in the days of his flesh, by his temptations in the wilderness, and agony with him in the garden; or rather by the heel of Christ is meant his human nature, which is his inferior and lowest nature, and who was in it frequently exposed to the insults, temptations, and persecutions of Satan, and was at last brought to a painful and accursed death; though by dying he got an entire victory over him and all his enemies, and obtained salvation for his people. The Targums of Jonathan and Jerusalem paraphrase this passage of the days of the Messiah, and of health and salvation in them: what is here delivered out in a way of threatening to the serpent the devil, carries in it a kind intimation of grace and good will to fallen man, and laid a foundation for hope of salvation and happiness: reference seems to be had to this passage in ( Psalms 40:7 ) "in the volume", in the first roll, (en kefalidi) , as in the Greek version, at the head, in the beginning "of the book, it is written of me, to do thy will, O my God."