Objective To explore the regulatory effect of TAK1 inhibitors on MAPK and NF-κB signaling pathway in diabetic rats and its renal protection mechanism. Methods A total of 48 rats accorded to the random number table method were divided into DN group, TAK1 group and control group,each group with 16 rats,control group with normal fed,DN group and TAK1 group by the intraperitoneal injection of 1% 50 mg/kg STZ DN model rat.8 rats were killed in each group at 4 weeks and 8 weeks respectively,the pathological changes of renal tissue were observed,serum TNF-α,MCP-1,IL-1β levels were detected by enzyme linked immunosorbent assay,p38MAPK,NF-κBp63 protein expression were detected by Western blotting,p38MAPK、NF-κBp63 mRNA levels in renal tissue were detected by real time fluorescence quantitative PCR. Results At 4 weeks and 8 weeks, the body weight, blood glucose and UAER of DN group and TAKl group were significantly higher than those in control group (P<0.05). The body weight and UAER of DN group were significantly higher than those of TAK1 group (P<0.05).The serum TNF-α,MCP-1,IL-1β levels in DN group and TAK1 group were significantly higher than those in control group(P<0.05),and DN group serum TNF-α,MCP-1,IL-1β levels were significantly higher than those in TAK1 group (P<0.05).The expression levels of p38MAPK,NF-κBp63 protein and mRNA in DN group, TAK1 group were significantly higher than those in control group (P<0.05), and p38MAPK,NF-κBp63 protein and mRNA in DN group was significantly higher than that in TAK1 group (P<0.05).Conclusions TAK1 induces inflammation by activating MAPK and NF-κB signaling pathways,and participates in diabetic renal injury.TAK1 inhibitors with anti-inflammatory effect by down regulate the expression of inflammatory factors.