To explore the effect of Yiqi Shengqing Fomula on TGF-β1/p38MAPK pathway in kidney tissue of diabetic rats. Methods:There were 60 SPF rats, among which 10 were in the normal group, and the rest were intraperitoneally injected with STZ to prepare DM models. After modeling, they were randomly divided into model group (equivalent distilled water), irbesartan group ［27 mg/(kg·d)］, low-dose Chinese medicine group ［3.465 g/(kg·d)］, middle-dose Chinese medicine group ［6.93 g/(kg·d)］, high-dose Chinese medicine group ［13.86 g/(kg·d)］, 10 rats in each group. After 8 weeks of administration, blood glucose, Scr, BUN were detected, renal pathology was observed, quantitative fluorescence PCR and immunohistochemistry were used to detect the expression of TGF-β1, p38MAPK, FN mRNA and protein. Results:After modeling, the blood glucose of each group was significantly higher than that of the normal group (P<0.01), but there was no significant difference between the groups (P>0.05). The serum BUN and Scr of rats in the model group were significantly increased (P<0.01), and the kidney tissue had a large amount of TGF-β1, p38MAPK, FN mRNA and protein expression (P<0.01); compared with the model group, the pathological damage of each treatment group was significantly reduced， Serum BUN and Scr were significantly reduced (P<0.01), TGF-β1, p38MAPK, FN mRNA and protein expression were significantly reduced (P<0.01), irbesartan group, middle and high-dose Chinese medicine group were better than low-dose Chinese medicine group (P<0.01). Conclusion:The activation of TGF-β1/p38MAPK pathway in diabetic rats leads to renal interstitial lesion. Yiqi Shengqing Fomula can reduce the expression of TGF-β1 and p38MAPK, thereby reducing the deposition of FN and protecting the kidneys.