Abstract： Objective To investigate the effect of Fosinopril,which has compensatory feature of dual elimination,on preventing and treating diabetic nephropathy in rats.Methods Rats were randomly divided into normal control group (C),streptozotocin diabetic group (D),diabetic rats treated with fosinopril [8mg/(kg·d)] group (M).Kidney weight/body weight,urinary volum,creatinine clearance rate (Ccr),urinary albumin and β 2-MG,urinary and serum ET-1 and TNF-α were measured at first,second and fourth week after treatment,the glomerular parameters were studied at the fouth week by using computer morphometric image analysis.Results Comparing with group C,kidney weight/body weight,urinary volum,Ccr,urinary albumin and β 2-MG in group D were increased significantly.The level of ET-1 in urine increased by 14 folds and by 0.2 folds in serum.Its elevation in urine was prior to in serum.TNF-α in urine increased also markedly but there was no change in serum.Significant decreasing in all above parameters were observed in group M compared with group D.Kidney morphometric image analysis showed that matrix and basement membrane area density decreased from 0.50±0.80 of group D to 0.25±0.02 of group M while capillary tuft area density increased from 0.50±0.08 to 0.77±0.02.Conclusion Fosinopril can significantly modify diabetic renal injury produced by glomerular hypertension and hyperfiltration,reduce urinary protein excretion,inhibit production of ET-1 and TNF-α in kidney and inhibit glomerular hypertrophies and mesangial matrix expansion.Fosinopril is very effective in preventing and treating diabetic nephropathy.