Objective To ascertain the role of NF?B and relationship among TGF?1,caspase-3 and apoptosis in CsA-induced nephrotoxicity.Methods Sixty-four wistar male rats were randomly divided into 4 groups:Vehicle,PDTC,CsA and CsA + PDTC group.The animals were daily subcutaneously injected either with CsA(15 mg/kg)or vehicle/PDTC(100 mg/kg).Four weeks later,BUN,serum creatinine,NAG and urine routine were examined.The kidneys were processed for light microscopy,immunohistochemistry and TENUL.Results A rat model of CsA-induced nephrotoxicity was established.CsA group showed significant increase in BUN,SCr and urine NAG compared with the controls,whereas CsA + PDTC group did not.Apoptosis is observered by TUNEL and the expressions of NF-?B,TGF-?1,caspase-3 increased significantly in CsA group compared with conrtol group.Whereas,both the apoptosis and the expressions of these proteins significantly decreased in rats treated with PDTC.Conclusion Apoptosis is induced in the CsA-induced chronic nephrotoxicity.Inhibition of NF-?B activation blockaded apoptosis and ameliorated CsA-induced chronic nephrotoxicity.The results suggest that NF-?B plays important roles in the progression of chronic CsA nephrotoxicity.