OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozoto-cin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were ran-domly divided into six groups:normal,model,Ton-gluo Digui decoction(high,medium,and low dose)and valsartan.Streptozotocin was injected intraper-itoneally to replicate the diabetic animal model.Af-ter 8 weeks,proteinuria was evaluated to establish the diabetic nephropathy model.Treatments were administered daily via the intragastric route.At 16 weeks after gavage,we determined 24 h urine pro-tein concentration,and blood glucose,serum creat-inine,and urea nitrogen concentrations.Then,rats were sacrificed,and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli,including glo-merular podocytes by transmission electron micros-copy.Western blot analysis was used to deter-mine the expression of nephrin,podocin,p62,be-clin-1,LC3 Ⅱ/Ⅰ,and p-mTOR/mTOR protein in kid-ney tissues.RESULTS:Compared with the model group,Ton-gluo Digui decoction was associated with decreas-es in 24 h urine protein concentration,and blood glucose,hemoglobin A1c,serum creatinine,urea ni-trogen concentrations,total serum protein and al-bumin.Concurrently,mesangial mesenteric broad-ening and fusion of foot processes were reduced,the glomerular basement membrane was not sig-nificantly thickened,and the number of podocytes and the number of autophagosomes in the podo-cytes was increased.Further,expression of nephrin,podocin,LC3 Ⅱ,and beclin-1 protein in kidney tis-sue was up-regulated,while expression of p62 pro-tein was down-regulated and mTOR phosphoryla-tion was inhibited.CONCLUSION:Tongluo Digui decoction may inhib-it the progression of diabetic nephropathy by inhib-iting mTOR phosphorylation,thereby increasing au-tophagy to protect podocytes and reducing pro-teinuria.