Cyclooxygenase (COX), an enzyme essential for prostaglandin biosynthesis, has two isoforms, COX-1 and -2. We investigated temporal and spatial changes in localization of these two COX proteins and mRNAs after excisional injury in rat skin. We also quantified the expression of these proteins and studied the effects of a specific COX-2 inhibitor on healing. Immunohistochemistry and in situ hybridization respectively indicated that the COX-2 protein and mRNA were expressed mainly within the basal layer of the epidermis, peripheral cells in the outer root sheath of hair follicles, and fibroblast-like cells and capillaries near epidermal wound edges. Much less intense expression was observed in normal skin than in injured skin. Western analysis demonstrated marked induction of COX-2 protein beginning within 12 hours and peaking 3 days after injury. In contrast, localization of COX-1 protein and mRNA, as well as the amount of protein expression, showed no significant change during wound healing. Administration of the COX-2 inhibitor delayed re-epithelialization in the early phase of wound healing and also inhibited angiogenesis. Thus, COX-2 induction may be important in cutaneous wound healing.