Abstract: Retinopathy is a major cause of morbidity in diabetes and remains the primary cause of new blindness. Therefore, it is necessary to find new drug to treat diabetic retinopathy. Type 2 diabetes mellitus (T2DM) rats were induced by injection (ip) with streptozotocin (STZ) 35 mg·kg^-1 and fed with a high-carbohydrate/high-fat diet 2 weeks later. From week 17 to 32, diabetic rats were given different doses of berberine 75, 150, and 300 mg·kg^-1, fenofibrate 100 mg·kg^-1 and rosiglitazone 4 mg·kg^-1, separately. Retinal structure was observed with hematoxylin-eosin staining and peroxisome proliferator-activated receptors (PPARs) α/δ/γ protein expressions were detected by immunohistochemistry. The retina of control rats was thicker than that of other groups, 16 weeks treatment with berberine (150 and 300 mg·kg^-1) and rosiglitazone 4 mg·kg^-1 thickened the diabetic retina, but no difference existed in retinal structure among groups. Both berberine (150 and 300 mg·kg^-1) and rosiglitazone 4 mg·kg^-1 significantly decreased PPARγ expression in diabetic retina; while berberine (150 and 300 mg·kg^-1) and fenofibrate 100 mg·kg^-1 obviously increased both PPARα and PPARδ expressions in diabetic retina. Berberine modulates PPARα/δ/γ protein levels in diabetic retina which may contribute to ameliorate retinopathy complication induced by STZ and a high-carbohydrate/high-fat diet. It is expected that berberine might be a more beneficial drug to treat diabetic retinal complication comparing with fenofibrate and rosiglitazone.