Objective To explore the possible mechanism of Yiqi Huoxue Decoction（益气活血方） in treating diabetic nephropathy. Methods Forty-two spontaneously diabetic rats（GK rats） were randomly divided into sham operation group

model group

and Yiqi Huoxue group

with 14 rats in each group. The model group and Yiqi Huoxue group were given high-calorie and high-fat diet as well as single nephrectomy to establish a diabetic nephropathy model. The kidneys in the sham operation group were not removed. Yiqi Huoxue group was given Yiqi Huoxue Decoction3. 125 g/（kg·d） for intragastric administration

and the sham operation group and model group were given 4 ml of distilled water for intragastric administration. After 8 weeks

the pathological morphology of the kidney was observed.The 24 h urine protein quantity and the expression of advanced glycation end products（AGE）

transforming growth factor-β（TGF-β） protein and mRNA in renal tissue were detected. Results The main pathological changes of renal tissue in each group were glomerular volume enlargement

mesangial cell and stromal hyperplasia

and tubular vacuolar degeneration. The changes in Yiqi Huoxue group were less significant than other groups

which were glomerular hypertrophy

mild mesangial matrix hyperplasia

and the renal tubular structure was basically normal. Compared with the model group

there were significant differences in the 24-hour urinary protein quantitation of the Yiqi Huoxue group at 3 weeks of gavage

6 weeks of gavage

and 8 weeks of gavage（P < 0. 01）. Yiqi Huoxue Decoction could significantly reduce the 24 h urine protein quantification of the model rats

and PASM

Masson positive rate

AGE

TGF-β protein expression and TGF-β mRNA were significantly decreased compared with the model group（P <0. 01）. Conclusion The mechanism of Yiqi Huoxue Decoction in treating diabetic nephropathy might be inhibiting the expressions of AGE

TGF-β and mRNA.