To evaluate the skin toxicity oj topical toluene application, toluene (35 mg/$cm^2$) was sequentially applied to the portion rat skin for five days. The topical toluene application resulted in increased xanthine oxidase activity and CYP content, and significantly decreased superoxide dismutase and glutathione peroxidase activities at five days in rat skin. Especially catalase activity was remarkably decreased in toluene-applied rat skin. And benzylalcohol dehydrogenase activity showed also a significant decrease in toluene-applied skin. On the other hand, histopathological ultrastructural examination revealed disrupted epidermal basement membrane, rared intercellular adhensions and degenerated keratin layer due to topical toluene application. Increased deposit of cerrous perhydroxide resulted from reaction with $H_2O_2$was abserved in toluene-treated animals. These results indicate that oxygen free radical may be responsible for ultrastructural changes in skin tissue by toluene application to rat skin.