Objective:To explore whether the renin antagonist SPH3127 inhibits angiotensin Ⅱ(Ang Ⅱ),Ang Ⅱ inhibits the ex-pression of transforming growth factor-β1(TGF-β1)and downregulates the transduction of the TGF-β/Smads signaling pathway,achie-ving a protective effect against hypertensive kidney injury.Methods:75 male SD rats were randomly divided into sham surgery group,model group,SPH3127 group,SB431542 group(TGF-β1 specific inhibitor),and valsartan group.Except for the sham surgery group,the other four groups were prepared with two kidneys one clip(2K1C)surgery method to establish a hypertension model.After success-ful modeling,the abdominal aorta serum and kidney tissue of the rats were continuously intervened for 4 weeks.ELISA was used to de-tect serum Ang Ⅱ and renal function indicators(creatinine,urea nitrogen concentration).HE staining,Sirius red staining,TUNEL and WT1 co staining were performed on kidney tissue for morphological observation.RT-qPCR and Western blot were used to detect TGF-β1,Smad3,and Smad7 mRNA in rat kidney tissue and the relative expression level of proteins,respectively.Results:After suc-cessful modeling,compared with the sham surgery group,the systolic blood pressure(SBP)of the tail artery in the model group,SPH3127 group,SB431542 group,and valsartan group increased(P＜0.05),but there was no statistically significant difference in SBP among these four groups(P＞0.05).After drug intervention,compared with the model group rats,the SPH3127 group,SB431542 group,and valsartan group all showed a decrease in SBP,Ang Ⅱ concentration,serum creatinine concentration,and urea nitrogen con-centration,degree of glomerular atrophy,collagen fiber deposition,podocyte apoptosis,TGF-β/Smads mRNA and protein expression lev-els(P＜0.05).Compared with the SPH3127 group,the SB431542 group showed a decrease in TGF-β/Smads mRNA and protein ex-pression levels(P＜0.05),an increase in SBP,Ang Ⅱ,and urea nitrogen concentrations(P＜0.05),an increase in collagen fiber dep-osition(P＜0.05),and an increase in podocyte apoptosis levels.Conclusion:SPH3127 can alleviate renal podocyte apoptosis and fi-brosis caused by hypertension by inhibiting the TGF-β/Smads signaling pathway by suppressing AngⅡ levels.