Objective:To investigate the nephroprotective effects of piperazine ferulate(PF) on 5/6 nephrectomized rats and explore its mechanism.Methods:32 subtotal nephrectomized SD rats were randomly divided into 4.groups:sham group, 5/6 nephrectomized group (NX group),NX+50 mg/kg Piperazine qernlate (PF) group and NX+25 mg/kg Fosinopril (F) group. After the operation, 50 mg/kg piperazine ferulate(PF group), 25 mg/kg Fosinopril (Fgroup) and water (Sham group and NX group) were delivered daily in same volume by gavage for 8 weeks, respectively. Urinary protein, BUN and serum creatinine were measured at the end of the study. Glomerulosclerosis index were evaluated by PAS and HE stain. Immunohistochemistry was used to examine the expression of fibronectin(FN) and collagen Ⅳ. RT-PCR was used to examine the transforming growth factor β 1(TGFβ 1) mRNA and tissue inhibitors of metalloproteinase 1(TIMP-1) mRNA in the cortex of the kidney.Results:Compared with the untreated 5/6 nephrectomized group (NX group),Urinary albumin excretion of pierazine ferulate and Fosinopril treated rats were substantially decreased (P<0.01), so were the serum creatinine and BUN. Pathohistological study revealed that, compared with the NX group, there were less glomerular matrix, type Ⅳ collagen and fibronectin in PF and F groups. Among the 5/6 nephrectomized rats, PF-treated group had the least renal changes in terms of glomerulosclerosis (P<0.05). The levels of TGF β 1 mRNA and TIMP-1 mRNA in all the treated rats were remarkably less than those of NX group (PF and F. vs. NX, P<0.05).Conclusion:PF can decrease the level of TGFβ 1 mRNA and TIMP-1 mRNA and reduce proteinuria and glomerulosclerosis in 5/6 nephrectomized rats. PF significantly prevents renal injury following subtotal renal ablation.