Sex differences on the effect of dose-dependent capsaicinoids on lipid metabolism were studied in rats. 24 rats of each sex were administered orally 0 mg/kg, 2.5 mg/kg, 5 mg/kg or 7.5 mg/kg capsaicinoids daily for 28 days. In male rats, body weight gained, and the levels of total lipids, total cholesterol and triglycerides in the liver were significantly decreased as the dose of capsaicinoids increased. On the other hand, plasma total cholesterol (TC), triglycerides (TG), HDL- and LDL-cholesterol concentration and liver weight were not affected by capsaicinoids. While in female rats, plasma TC, TG, HDL-C and LDL-C concentration, liver total lipids, TC and TG concentration were significantly decreased as the dose of capsaicinoids increased. The mRNA level of hepatic TRPV1, ileac ASBT and IBABP were increased as the dose of capsaicinoids increased in all rats groups. The mRNA level of hepatic HMG-CoA reductase, CYP7A1 and FXR were significantly decreased in female rats groups. These results show that the hypocholesterolemic effect of capsaicinoids in dose-dependent manner in rats was mediated by inhibited synthesis of endogenous cholesterol, female rats were more sensitive than male rats on hypolipidemic effect of capsaicinoids.