Objective：To investigate the effects of Berberine（Ber） on lipids metabolism and atherosclerosis in hyperlipidemic rabbits and to study the possible mechanism. Methods：The hyperlipidemic rabbit model was established by feeding high fat diet for 2 months. 40 New-Zealand rabbits were randomly divided into control group，high fat diet model group，high fat diet and Ber treated group[28，112 mg/（kg·d）]，high fat diet and Fenofibrate treated group[30 mg/（kg·d）]. The levels of serum total cholesterol（TC），triglycerides（TG），low density lipoprotein-cholesterol（LDL-C） and high density lipoprotein-cholesterol（HDL-C） were determined after 2 months，pathomorphological changes of aortic arteries was observed and inductible nitric oxide synthase（iNOS） and scavenger receptor class-B type 1（SR-B1） mRNA expression in aortic tissue were quantified by quantitative real time PCR. Results：The levels of serum TC，TG and LDL-C were obviously elevated（P<0.05），apparent atherosclerotic plaque was observed in aortic arteries and iNOS and SR-B1 mRNA expressions were obviously increased（P<0.05） in high fat diet group compared with those in control group. Serum TC，TG and LDL-C levels were decreased（P<0.05），HDL-C level was increased（P<0.05），degree of aortic atherosclerosis was mitigated，foam cells were reduced and iNOS activity and SR-B1 mRNA expressions were reduced（P<0.05） in high fat diet and Ber treated group than in high fat diet model group. Conclusions：Ber can obviously reduce the blood lipid levels and aortic atherosclerosis in the hyperlipidemic rabbits. The mechanisms may be related with the down-regulation of the iNOS and SR-B1 mRNA expressions.