Aim To study the effect of thalidomide on the atherosclerotic lesions induced by abnormal shear stress in the carotid arteries of New Zealand Rabbits. Methods After assembled silastic collars (length 8 mm,intra-diameter 1.4 mm) around the right carotid arteries of all the New Zealand White rabbits,they were randomly divided into three groups:control group (chew diet,n=13),high-fat group (with 2% cholesterol,n=13) and high-fat added with thalidomide (20 mg/kg) group. The rabbits were fed for 9 weeks. Serum was collected at the first week and the end week. Plasma triglyceride (TG),total cholesterol (TC),high density lipoprotein (HDL),and low density lipoprotein (LDL) were determined by commercially enzymatic methods. the atherosclerotic lesions in carotid arteries were determined by using Sudan Ⅳ staining and HE staining. Results There was no obvious difference in body weight between three groups before and after experiment. Plasma TG,TC,LDL and HDL concentrations were markedly increased in high-fat group and high-fat added with thalidomide group compared with Control (P<0.05). Compared with high-fat group,the content of TC,LDL,HDL and TG in high-fat added with thalidomide group had not statistical difference. Plaques were identified to exist in the upstream from the cast obviously more than downstream from the cast in sizes in high-fat group with Sudan Ⅳ staining. The atherosclerotic lesions in high-fat added with thalidomide group existed in the upstream mainly,and the sizes were less than that in high-fat group. Compared with no atherosclerotic lesion in the cast,there were lipid accumulation and cells infiltration in atherosclerotic lesions in high-fat group with HE staining,which extended to the lumina. The atherosclerotic lesions in the downstream existed with neointima formation. The main lesion in high-fat added with thalidomide group was neointima formation in the upstream,and no obvious lesion in downstream and the cast. There were no lesions the carotid arteries in the control group. Conclusion Abnormal shear stress may induce the atherosclerotic lesion formation in the carotid arteries in New Zealand Rabbits,and which could be inhibited by thalidomide.