Aim To explore the effects of probucol on the plaques formation of aorta and soluble thrombomodulin in hypercholesterolemic rabbits. Methods 16 male New Zealand white rabbits were fed with 1% cholesterol, 7.5% protein,8% lard diet for 8 weeks,and then were randomly divided into two groups.Starch group(n=8): maintained cholesterol and starch(500 mg/kg everyday) diet for 6 weeks;probucol group(n=8): the same cholesterol diet supplemented with(500 mg/kg everyday) probucol for 6 weeks;and control group(n=8) was fed with normal diet for 14 weeks.The soluble thrombomodulin concentrations were detected by enzyme-link-immuno sorbent assay,and the histopathological changes of the aortas were detected at the end of the study. Results Compared with control group,rabbits fed with high cholesterol diet showed higher levels of serum total cholesterol,low-density lipoprotein cholesterol and high-density lipoprotein cholesterol,all of which were significantly reduced by probucol treatment.There were atherosclerotic lesions in aortas in starch group as compared with control group.The areas of the plaque(51.54%±8.32%) and the intima thickness(0.58±0.17 mm) of the aorta were ameliorated in probucol group as compared with starch group(84.81%±9.35%,1.62±0.18 mm,respectively).The base concentrations of soluble thrombomodulin in the three groups were very low. The levels of sTM were significantly increased after 10 weeks of high-cholesterol diet in starch group,and probucol significantly reduced the level of soluble thrombomodulin(3.25±0.52 μg/L) as compared with starch group(7.56±0.62 μg/L) at the end of the study.The concentration of soluble thrombomodulin was positively associated with the plaques areas of aorta(r=0.72,P=0.008). Conclusions Probucol decreased the plasma cholesterol and soluble thrombomodulin concentrations and protected the endothelial function,which may inhibit the formation of plaques of aortas in cholesterolemic rabbits.