Abstract: Objective To investigate role of Fosinopril (Fos) and Valsartan (Val) on klotho gene expression induced by Ang II and the relationship between klotho and TGF-β1. Motheds Culture cells, NRK-52E, were incubated with medias such as Ang II, Fos and Val. Five groups, control, AngII(10-7mol/L), AngII(10-7mol/L)+Fos(10-5mol/L), AngII(10-7mol/L)+Val(10-5mol/L) and AngII(10-7mol/L)+Fos(10-5mol/L)+Val (10-5mol/L) , were divided to observe the expression of the klotho and TGF-β1 mRNA and protein. The klotho and TGF-β1 mRNA were detected by reverse transcription – polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and Western Blotting (WB) was applied to determine the klotho and TGF-β1 protein expression. The linear relationship between klotho and TGF-β1 protein expression was analyzed by Pearson’s. Results 1. AngII induced an up-regulated expression of TGF-β1 mRNA , and associated with down-regulated klotho mRNA in NRK-52E as compared to control (all P＜0.05); in cells incubated with Fos or Val or booth of all, the klotho mRNA expression was enheanced, and the TGF-β1 mRNA expression was diminished as compared to the AngII group(all P＜0.05); combined Fos and Val could not enhance the expression of klotho gene, no significant different was showed as compared to the Fos group and Val group. 2. IHC and Western Blotting revealed that klotho protein was increased, TGF-β1 protein was decreased in Fos group, Val group and combination group as compared to AngII group, but no significantly different among the three groups was showed as compared to the Val group or Fos group. 3. Negative relationship was showed between klotho and TGF-β1 protein expression(r=-0.717, P＜0.05). Conclusions Fosinopril and Valsartan can enhance the expression of klotho gene, and down-regulate TGF-β1 expression in NRK-52E, the increased level of klotho expression may be one of the important factor for preventing the renal fibrosis induced by TGF-β1.