Abstract: The objective of this study was to characterize the difference in antihypercholesterolemic effect between simvastatin and ezetimibe in high-fat-fed golden hamsters model.A total of 40 healthy male golden hamster were randomly assigned to the following four groups:normal control group,hyperlipidemic model group,simvastatin group and ezetimibe group.The normal control group fed the normal diet and the other three groups fed a high-fat diet.The simvastatin group and ezetimibe group were intragastrically administrated 3 mg/(kg·BW)of simvastatin and 2.5 mg/(kg·BW)of ezetimibe for consecutive nine weeks,respectively,and the normal control group and hyperlipidemic model group were received distilled water contemporaneously.At the end of the experiment,the body weight of the golden hamsters was determined and their liver were sampled and weighted to calculate the ratio of liver weight to body weight;the histological sections of liver were prepared and were stained with HE method;the pathological changes of liver tissues were observed using light microscopy.The results showed that the simvastatin group had extremely significantly higher liver weight compared to normal control group(P<0.01),while the liver weight of ezetimibe group had no significant difference with normal control group(P>0.05);extremely significantly higher ratio of liver weight to body weight was observed in simvastatin group compared to normal control group(P<0.01),and the ratio of liver weight to body weight in ezetimibe group were found significantly reduced compared to normal control group(P<0.05);the simvastatin group had similar pathological changes of liver observed by naked eye to hyperlipidemic model group:the liver was earth yellow colored with granular feeling in surface and the edge was sharp;similar pathological changes of liver observed by naked eye were observed in ezetimibe group and normal control group:the liver was dark brown colored with soft texture and the edge was also sharp;under light microscopy,simvastatin group showed intracytoplasmic fat vacuoles within perihepatic margin cells which squeezed the cell nuclear to a side of the cell,and vacuolar degeneration and inflammatory cell infiltration were also observed;the liver cells of ezetimibe group was homogeneous and eosinophilic with abundant cytoplasm,no intracytoplasmic fat vacuoles,vacuolar degeneration or inflammatory cell infiltration were observed,and the hepatic cord arranged regularly.In conclusion,ezetimibe had superior antihypercholesterolemic effect in high-fat-fed golden hamsters model to simvastatin.