This study was conducted to investigate the effect of dietary grape skin on lipid peroxidation and antioxidant defense system in rats fed high fat diet. The Sprague-Dawley rats were fed either control (5% fat) diet or high fat (25% fat) diet which was based on AIN-93 diet for 2 weeks, and then they were grouped as control group (C), control + 5% grape skin group (CS), high-fat group (HF), high fat + 5% grape skin group (HFS) with 10 rats each and fed corresponding diets for 4 weeks. The hepatic thiobarbituric acid reacting substances (TBARS) were increased in high fat group as compared with control group, but reduced by grape skin. The serum total antioxidant status, and activities of hepatic catalase and superoxide dismutase, xanthine oxidase and glucose-6-phosphatase were increased by supplementation of grape skin. Glutathione peroxidase activity was significantly higher in CS group than in C group. Grape skin feeding tended to increase the concentration of total glutathione, especially in control group. The ratio of reduced glutathione to oxidized glutathione was lower in high fat groups than in control groups. The ratio was increased by dietary supplementation of grape skin in control group. These results suggest that dietary supplementation of grape skin would be effective on protection of oxidative damage by lipid peroxidation through improvement of antioxidant defense system in rats fed high fat diet as well as rats with low fat diet.