Objective To study the preventive effect of spironolactone on renal tubulointerstitial fibrosis of diabetic nephropathy (DN)in rats.Methods Sixty adult SD rats were random divided into sham operation group(C),diabetic nephropathy group(D)and spironolactone interventional group(A).After diabetes WaS induced by administrating strep tozotocin(STZ),spironolactone was perfused into the stomach of rats in group A.On the 7th,14th,21st,28th days after treatment,rats were put to death,their kidneys were removed to observe the expressions of TGF-β1 and MMP-9 by immunohistochemistry method.The blood potassium,natrium,glucose, serum creatinine,cholesterol,triglyceride and urinary albumin quantification were measured.Results Urine protein in group A wag lower than that in group D.The blood potassium,natrium,glucose,serum creatinine,cholesterol and triglyceride had no difference between group A and group D(P＞0.05).Compared with group D,the expressions of TGF-β1 in group A Was decreased(P＜0.01),the expressions of MMP-9 in group A was hisher than that in group D(P＜0.01).Conclusion Spironolactone could decrease the expression of TGF-β1 and increase the expression of MMP-9 in the tubulointerstitial of diabetic nephropathy,which may delay the progress of renal tubulointerstitial fibrosis.