Aim To explore the effect of auricularia auricula polysaccharide on the proliferation of vascular smooth muscle cells in the formation of atherosclerosis. Methods Thirty New Zealand white rabbits were randomly divided into three groups: normal group, model group and experiment group with ten rabbits in every group. The period of experiment is twelve weeks. Normal group received normal chow.model group received normal chow and cholesterol and, experiment group received normal chow,cholesterol and Polysaccharide. The levels of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholester (LDLC), high density lipoprotein cholesterol (HDLC), malondialdehyde (MDA) and supperoxide-dismutase (SOD) were detected at 0 and 12th week. Animals were killed after 12 weeks, and excised artery segments were prepared for histomorphological observation and α-smooth muscle actin was investigated by immunohistochemistry analysis. The images were analyzed with HAIPS1000 software to distinguish the express of α-smooth muscle actin. Results The serum TC, TG, LDLC and MDA were decreased (model group versus experiment group: TC was respectively 18.76±2.32 and 11.68±1.63; TG was respectively 1.52±0.15 and 1.19±0.12; LDLC was respectively 17.62±2.27 and 9.64±1.56; MDA was respectively 4.53±0.21 and 4.14±0.14,p<0.01 or p<0.05), while the levels of serum HDLC and the serum SOD concentration were increased (model group versus experiment group: HDLC was respectively 0.65±0.09 and 0.73±0.76; SOD was respectively 182.29±10.87 and 215.97±7.38, p<0.01 or p<0.05) in experiment group compared with those in model group. The atherosclerotic lesion were alleviated (model group versus experiment group: 0.44±0.10 and 0.30±0.83, p<0.01) and smooth muscle cells also diminished in lesions (model group versus experiment group: 14%±1% and 12%±1%, p<0.05). Conclusion The proliferation of vascular smooth muscle cells can be decreased through Auricularia Auricula Polysaccharide, thus inhibits the formation of atherosclerosis.