Objective To investigate the protective effects of Jiangtangyishen Decoction on early-stage diabetic nephropathy of MKR mice. Methods Twenty-four MKR mice were randomly divided into three groups after stratification by sex and fasting plasma glucose, i.e. the model group, traditional Chinese medicine (TCM) group with Jiangtangyishen Decoction 16.72 g/(kg?d), western medicine group with Gliquidone 4.33 mg/(kg?d) and Benazepril 1.44 mg/(kg?d). In the same period, the C57BL/6 wilding mice were the normal group. After treated for 30 days, the levels of blood glucose, the content of microalbuminuria and ?2-microglobulin in urine were observed by ELISA. Renal pathologic lesion of each group were observed by light microscopy and electron microscopy. Results After treated for 30 days, TCM group had significant effect of decreasing fasting blood glucose, discharge of microalbuminuria and ?2-microglobulin in urine of MKR mice (compared with that before treated, P