The aim of the study was to investigate the anti-obesity effect of Coprinus comatus (CC) in high-fat diet-fed Zucker rat (fa/fa). Obesity was induced by feeding on high-fat diet (HFD) containing 60% kcal fat for 10 weeks, in which CC extracts were administrated through the gastrointestinal tract at a concentration of 200 mg/kg BW/day for 10 weeks. The total polyphenol and flavonoid contents of CC extracts were found to be $18.5{pm}1.1mg$ of catechin equivalent/g, and $5.24{pm}0.54mg$ of quercetin equivalent/g extract, respectively. The DPPH, ABTS, and hydroxyl radical scavenging activities of CC extracts were 15.34 %, 17.25%, and 16.18%, respectively. In animal study, CC administration significantly reduced the body weight, while there were no significant differences in the daily food intake between the HFD-fed Zucker rats and HFD plus CC-fed rats. CC treatment decreased epididymal and perirenal fat weights in HFD-fed Zucker rats. Significant decreases in the levels of triglyceride and total cholesterol in the serum and liver were observed in the CC-treated group compared with HFD-fed Zucker rats. Serum HDL-cholesterol levels in the CC-treated group were increased compared with the HFD-fed groups. Serum AST and ALT activities in the CC group were significantly lower than those of the HFD-fed group. Taken together, these data demonstrated that CC has potential in preventing high-fat diet induced obesity and is a good candidate for an anti-obesity agent.