Objective To study the effects and mechanisms of Exendin-4 on streptozotocin-induced diabetic nephropathy in rats. Methods 60 SD healthy rats without specific pathogen level were selected. 45 rats were established to establish diabetic nephropathy model. They were randomly divided into model group, benazepril group, Exendin-4 low, medium and high dose group, and the blank group was healthy rats with 9 rats in each group. After successful modeling, benazepril group was given 10 mg / kg benazepril tablets by gavage, exendin-4 low, medium and high dose groups were injected subcutaneously with Exendin-4 4, 20 and 100 g / kg respectively, and the normal group and model group were given purified water by gavage. One week after administration, total cholesterol (TG), triglycerides (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), amylase (AMY) and blood glucose (BG) were measured, hemoglobin ( HbAlc), fasting serum insulin ( FINS), body mass, renal index ( RI ), glomerular area, glomerular diameter and the expression of advanced glycation end products (AGEs), PDK1, p-Akt and p-mTOR proteins in renal tissue. Results The expression of TG, TC, LDL, BG, HbAlc, fins, ages, body mass, RI, glomerular area, glomerular diameter, PDK1, p-Akt, p-mTOR protein expression in the middle and high dose groups were lower than that in the low dose group (P<0. 05). The expressions of TG, TC, HDL, LDL, BG, HbAlc, FINS, AGEs, RI, glomerular area, glomerular diameter, PDK1, p-Akt and p-mTOR protein in Exendin-4 high dose group were lower than those in Exendin-4 medium dose group, and HDL was higher than that in Exendin-4 medium dose group. There were significant differences in TC, HDL, LDL, AMY, HDL, body mass, RI and glomerular area ( P< 0.05) Conclusions Exendin-4 can reduce inflammation levels in streptozotocin-induced diabetic nephropathy rats and improve their BG, lipid levels, and pancreas function. The mechanisms underlying these effects may be related to inhibition of the PDK1 / Akt / mTOR pathway. These findings provide a new direction for the clinical treatment of diabetic nephropathy and other inflammatory diseases.