Aim To explore the effects of probucol on liver protection and PPARα expression of atherosclerosis rabbits model. Methods 16 male New Zealand white rabbits were fed with 1% cholesterol,5% lard diet for 8 weeks,and then were randomly divided into two groups:high-fat group:maintained cholesterol diet for 6 weeks; probucol group:the same cholesterol diet mixed with 0.25 g/d probucol for 6 weeks. Control group was fed with normal diet for 14 weeks. This study detected the change of serum lipid profile,atherosclerotic plaque areas of aortas,histopathology and PPARα mRNA and protein expression of the livers at the end of the study. Results After 6 weeks treatment of probucol,the levels of total cholesterol (TC),high density lipoprotein cholesterol (HDLC),and low density lipoprotein cholesterol (LDLC) were reduced significantly compared with the high-fat group (P><0.05). The atherosclerotic plaque area of aortas and the histopathology of fatty liver were ameliorated in probucol group compared with high-fat group. The PPARα mRNA and protein expressions in the fatty livers of high-fat group were downregulated compared with control group,and probucol upregulated PPARα mRNA and protein expressions. Conclusion Probucol decreased the serum cholesterol and upregulated PPARα mRNA and protein expressions,which may inhibit the formation of plaques of aorta and fatty liver in atherosclerosis rabbits model.