The present study was to investigate the mechanisms by which hawthorn fruit lowers serum cholesterol in hamsters. The control group was fed a semisynthetic diet containing 0.1% cholesterol while the tested group was maintained on the same diet but supplemented with 0.5% hawthorn fruit aqueous ethanolic extract for 4 weeks. Serum total cholesterol (TC) and triacylglycerols (TG) were decreased by 10 and 13%, respectively, in hawthorn fruit group as compared with the control (P<0.05). Supplementation of hawthorn fruit aqueous ethanolic extract led to greater excretion of both neutral and acidic sterols. Further enzymatic assays suggest the mechanisms by which hawthorn fruit decreases serum cholesterol involve a greater excretion of bile acids mediated by up-regulation of hepatic cholesterol 7α-hydroxylase (CH) activity, and an inhibition of cholesterol absorption mediated by down-regulation of intestinal acyl CoA:cholesterol acyltransferase (ACAT) activity.