To investigate the skin toxicity of xylene, xylene (25 mg/$ extrm{cm}^2$) has been sequentially applied to the rat skin for four days. On the light microscopic examination, epithelium was left out with infiltration of inflammatory cells in border with dermis, and formation of new epithelial layer was shown under the inflammatory zone. Application of xylene to the rat skin showed the marked rise of cutaneous xanthine oxidase activity whereas, He activities of oxygen free radical scavenging enzymes, superoxide dismutase and glutathione S-transferase, were significantly declined. Furthermore, the content of cutaneous glutathione was more and less decreased in rat skin applied with xylene. In conclusion, these results suggest that a part of oxygen free radical may be responsible for morphological changes in skin by applying xylene to the rat skin.