Cyclooxygenase-2 (COX-2) and the prostaglandin products generated as a result of COX-2 activity mediate a variety of biological and pathological processes. Scarless healing occurs in fetal skin in the first and second trimesters of development. This scarless healing process is known to proceed without a significant inflammatory response, which appears to be important for the lack of scarring. Because the COX-2 pathway is an integral component of inflammation, we investigated its role in the fetal repair process using a mouse model of scarless fetal wound healing. COX-2 expression in scarless and fibrotic fetal wounds was examined. In addition, the ability of exogenous prostaglandin E(2) to alter scarless fetal healing was evaluated. The results suggest that the COX-2 pathway is involved in scar production in fetal skin and that targeting COX-2 may be useful for limiting scar formation in adult skin.