When epidermal growth factor (EGF) ointment containing a protease inhibitor, nafamostat (NM), was applied to burn sites in rats, the superoxide dismutase (SOD) enzyme activity and protein content increased 45% and 60%, respectively, at these sites 1 d after the burns compared with the control ointment. Following treatment with EGF plus NM (EGF + NM) ointment, messenger RNA for SOD also increased, to about 1.6 times that of the control at 1 d after the burn, indicating that this ointment stimulates SOD synthesis at burn sites in vivo. In contrast, following treatment with EGF + NM ointment, the content of heat shock protein (HSP 70) in the burned tissue decreased to about 70% of the control value 1 d after the burn. These findings suggest that EGF + NM ointment alleviated tissue damage at burn sites at an early stage, and that this was related to the stimulation of SOD synthesis and reduced HSP 70 levels. We also examined the effects of SOD ointment on wound healing at burn sites. A dose-dependent increase in the dry weight of granulation tissue at wound sites 3 d after the burn was observed following the application of this ointment. These results suggest that SOD may play an important role in wound healing after burns.