Aim To evaluate the protective effects and possible mechanisms of probucol on atherosclerosis in hyperlipidemic type 2 diabetic mice. Methods The hyperlipidemic type 2 diabetic （db/db-LDLR^－/－） mice were generated by the cross between leptin receptor deficient （db/db） mice and low density lipoprotein receptor knockout （LDLR^－/－） mice.8-week-old db/db-LDLR^－/－ mice were fed with high fat diet （HFD） mixed with 0.5% probucol,diabetic （db/db-LDLR^－/－） and non-diabetic （LDLR^－/－） control mice were fed with the same HFD without probucol addition.At 2 and 4 months after HFD,plasma lipids and glucose levels were measured.At 4 months after HFD,glucose tolerance and “en face” total aortic atherosclerotic plaque sizes were measured. Results Compared with type 2 diabetic HFD control group,probucol had strong protective effects on reducing plasma total cholesterol （TC）,triglyceride （TG）,glucose levels,improving glucose tolerance,and decreasing atherosclerotic lesions.Meanwhile,high density lipoprotein cholesterol （HDLC）/TC levels were unchanged. Conclusions Probucol had striking antiatherogenic effects under type 2 diabetic condition with hyperlipidemia.It might be an effective therapy in type 2 diabetic macrovascular disease.