Abstract: OBJECTIVE To explore intervention of Gualou Qumai Tang(GLQM) in preventing the development of diabetic nephropathy(DN) through P38MAPK signaling pathway methods. METHODS Except those in the normal group， SD rats of DN model were established by with unilateral nephrectomy and intraperitoneal injection of streptozotocin(STZ) induced production.Then rats were randomly divided into five groups: the model group， and the four treated groups treated with low dose of GLQM-L， medium dose of GLQM-M， high dose of GLQM-H， positive medicine (valsartan)， The treatments were given via gastrogavage every day starting from the 4th week of modeling， groups treated with high， medium and low dose of GLQM were given via gastrogavage to 5.6， 2.8， 1.4g/kg，positive drugs (valsartan) group were given via gastrogavage to 4.8×10g/kg， the normal group and model group were given 2.8g/kg distilled water， once a day for 12 weeks. we observed the sign of rats and the rat glomerular， renal tubular structure changes with the optical microscope. Then we observed the sign of rats and the expreion the basic fibroblast growth factor(bFGF)， Insulin-like Growth Factor(IGF)， Monocyte Chemotactic Protein-1(MCP-1) changes in renal issues of rats by using ELISA. The protein expression of p-p38MPK， p-CREB， FN were immunohistochemically investigated. The mRNA expressions FN in renal tissue we examined using qPCR method. The protein expression of p-p38MPK， p-CREB， FN in renal tissue we also examined using Western Blot method. RESULTS The pathologic changes of the renal tissue apparented in the model group. The bFGF， IGF， MCP-1 in renal tissues of rats with model were higher than the nomal group， there were significant difference among the model group and the norml group(P<0.01). The bFGF， IGF， MCP-1 in renal tissues of rats with GLQM and valsartan were lower than the model group， there were significant difference among them(P<0.05~0.01). The protein expression of p-p38MAPK， p-CREB， FN in renal tissues with model were higher than the normal group(P<0.05~0.01). The mRNA expression of FN in renal tissues of rats with GLQM were lower than the model group(P<0.05~0.01); the protein expression of p-p38MAPK， p-CREB， FN in renal tissue of rats with GLQM were lower than the model group(P<0.05~0.01). CONCLUSION GLQM can reatrain the activation of p38MAPK signaling pathway and be effective in repair and regeneration of the damaged tissue， it is also slow down the process of DN.