Collagenase-3 (matrix metalloproteinase 13, MMP-13) was employed as a surrogate marker to compare the characteristics of incisional wound repair after surgery with the free-electron laser at 6.1 microm and the scalpel. Using a transgenic mouse strain with the MMP-13 or the COL1A2 promoter driving luciferase expression, we observed MMP-13 and COL1A2 expression, tensile strength, macrophage infiltration, and wound histology for up to 62 d. The scalpel incisions showed higher tensile strength than free-electron laser wounds from days 10 to 22 postwounding, despite minimal collateral thermal damage. After 45 d healing was similar. Trichrome staining confirmed that the scalpel incisions had more dense collagen deposition than free-electron laser incisions up to 36 d postinjury, but at day 45 they became similar. MMP-13 expression was biphasic, with peak activities at days 15 and 37 after injury, whereas free-electron laser wounds showed greater luciferase activity than scalpel wounds. Peak COL1A2 activity preceded the MMP-13 maximum. MMP-13 expression localized predominantly to dermal fibroblasts near the epidermis at day 15, and in the region of the deep dermis, muscle, and fascia at day 37 postwounding. Migrating muscle cells, but not all skeletal muscle cells, also expressed MMP-13. Free-electron laser incisions contained more macrophages than scalpel wounds at days 2 and 7 postinjury, suggesting that free-electron laser irradiation exacerbated the inflammatory response and thereby stimulated MMP-13 expression. These results revealed that MMP-13 was involved in a series of coordinated events during wound healing, not only the long-term remodeling of wound connective tissue, but also skeletal muscle repair. MMP-13 activity in vivo may correlate with the extent of tissue damage.