Aim To observe the effect of probucol on the expression of heme oxygenase-1(HO-1)protein in atherosclerotic lesions and livers in rabbits. Methods The hypercholestrolemic model was built up by 8 weeks high cholesterol diet.Then 16 New Zealand rabbits were randomly fed with starch(n=8,starch group) or probucol(n=8,probucol group) for 6 weeks.Those two groups and another 8 New Zealand rabbits(n=8,control group) were tested for serum lipid,body weight and serum malon dialdehyde(MDA).Expression of HO-1 was detected by immunohistochemistry. Results Probucol treatment increased HO-1 expression in atherosclerotic plaque,aorta smooth muscle cell and liver,decreased atherosclerotic areas,initma thicknesses,and ratio of intimae to media,and down regulated serum total cholesterol(TC),low density lipoprotein cholesterol(LDLC),high density lipoprotein cholesterol(HDLC) and MDA.Expression of HO-1 protein in atherosclerotic plaque,smooth muscle cell and liver in hypercholesterolemic rabbits with and without probucol treatment was negatively correlated with serum levels of MDA,atherosclerotic areas,intimae thickness,and the ratio of intimae to media(P<0.05). Conclusions While lowering serum cholesterol,probucol may also exert anti-oxidative actions through upregulation of HO-1 expressions,which might be an important part of its anti-atherogenic properties.