Aim: To study the effect and mechanism of lycium barbarum polysaccharide(LBP) against atherosclerosis in rabbits. Methods: Thirty-six healthy New Zealand white rabbits were randomly divided into three groups.Control group was fed with normal food,model group was fed with 1.5% cholesterol,and LBP group, 1.5% cholesterol plus 3.0 mg/kg LBP celiac injection. After ten weeks,the concentrations of triglyceride(TG),total cholesterol,high density lipoprotein cholesterol(HDL-C),C reactive protein(CRP),nitric oxide(NO),MDA,and the activity of SOD of each group were measured. Results: Compared with the control group,concentrations of TG,TCh,NO,MDA,and CRP of model group increased significantly(P<0.01),and activity of SOD and HDL-C/TCh decreased(P<0.01). Compared with the model group,concentrations of TG,NO,MDA,and CRP of LBP group significantly lowered(P<0.01 or 0.05), while the activity of SOD and HDL-C/TCh increased(P<0.01). Conclusion: LBP can effectively increase the activity of SOD against oxidation,regulate immunity,and elevate the radio of HDL-C/TCh.LBP is a potential drug in treating and preventing atherosclerosis.