Objective To investigate the therapeutic effects and mechanisms of Nephropathy FormulaⅠ(NF-Ⅰ)in rats with chronic renal failure(CRF).Methods A CRF model was established using continuous adenine gavage.After successful modeling,the rats were randomly divided into normal group,model group,low-dose and high-dose of NF-Ⅰ groups,with 10 rats in each group.The group-specific interventions were administered.Renal histopathological changes were observed via hematoxylin-eosin(HE)staining,renal fibrosis was evaluated using Masson staining,collagen Ⅳ(Col-Ⅳ)expression in renal tissues was detected by immunohistochemistry,and protein expression of focal adhesion kinase(FAK),Ras,and mitogen-activated protein kinase(MAPK)in renal tissues was analyzed via Western Blot.Additionally,in vitro experiments were performed to validate the effect of NF-Ⅰ on the FAK-Ras-MAPK signaling pathway.Results Compared with the normal group,the model group exhibited a significant increase in renal interstitial fibrosis area and elevated protein expression levels of Col-Ⅳ,FAK,Ras,and MAPK in renal tissues,and the differences were statistically significant(P＜0.05).In comparison to the model group,both the NF-Ⅰ low-dose and high-dose groups showed significant reductions in renal interstitial fibrosis area and downregulation of Col-Ⅳ,FAK,Ras,and MAPK protein expression levels,and the differences were statistically significant(P＜0.05),while the effects in the high-dose group were superior.In vitro validation results demonstrated that,compared with the control group,the protein expression levles of cellular FAK,Ras and MAPK were decreased in drug-containing serum group(P＜0.05).Conclusion NF-Ⅰeffectively ameliorates renal fibrosis in CRF rats,potentially through suppression of the FAK-Ras-MAPK signaling pathway.