Objective To research the molecular mechanism of Qiwei Granules [granules of Huangqi （Radix Astragali） and Weimao （Euonymi Ramulus）] to treat interstitial fibrosis in diabetic nephropathy （DN）. Methods KK-Ay mice with spontaneous type 2 diabetes were fed with high-fat fodder to establish DN models. Forty-five successful model mice were randomized into model group

Chinese medicine group and western medicine group

with 15 in each. The Chinese medicine group was gavaged with 20 g/（kg·d） crude drug of Qiwei Granules and the western medicine group was gavaged with 10 mg/（kg·d） valsartan capsules. Fifteen male C57BL/6J mice were chosen as the normal group. The administration lasted for 12 weeks. The expressions of transforming growth factor-β1 （TGF-β1）

phosphorylated-Smad2 （P-Smad2）

P-Smad3

Smad7

integrin-linked kinase （ILK） and ILK mRNA were examined with immunohistochemistry

Western blot and quantitative real-time polymerase chain reaction respectively. Results Comparing with the normal group

the expressions of TGF-β1

P-Smad2

P-Smad3

ILK and ILK mRNA in the model group were significantly increased （P<0.01）

but the expression of Smad7 was significantly decreased （P<0.01）. Comparing with the model group

the expressions of TGF-β1

P-Smad2

P-Smad3

ILK and ILK mRNA in both administration groups were significantly decreased （P<0.05 or P<0.01）

but the expression of Smad7 was significantly increased （P<0.01）. Comparing with the western medicine group

the expression of P-Smad3 was significantly increased in the Chinese medicine group （P<0.05）. Conclusion Qiwei Granules can block TGF-β1/Smads signaling pathway and delay the progression of renal interstitial fibrosis by down-regulating the expressions of TGF-β1

P-Smad2

P-Smad3 and ILK and up-regulating the expression of Smad7.