The present study was designed to investigate the effect of umbelliferone (UMB) on insulin resistance (IR) and oxidative stress in rats fed a high fructose diet (HFD). Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the UMB at three different doses (10, 20 and 40mg/kg, p.o) from the 16th day. At the end of 60 days, HFD rats exhibited significant increases in plasma glucose and insulin levels. The activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and the levels of non-enzymic antioxidants such as vitamin C, vitamin E and reduced glutathione were decreased while increases in the levels of lipid peroxidative markers were observed in liver tissues of HFD rats as compared to control rats. In addition, rats fed a HFD with UMB reversed all the above changes to near normal in a dose dependent manner. The effect at a dose of 40mg/kg b.w/day was more pronounced than the other two doses (10 and 20mg/kg b.w/day). Biochemical findings were supported by histological studies. These results indicated that administration of UMB may be a feasible therapeutic strategy for prevention of a high-fructose diet-induced insulin resistance and oxidative stress.