Selaginella uncinata (Desv.) Spring, known as Cuiyuncao, is a traditional Chinese prescription against some inflammation related diseases. To examine the effect of Cuiyuncao on renal fibrosis in a rat model and the underlying mechanism, a renal fibrosis rat model was established via unilateral ureteral obstruction (UUO). Flow cytometry was used to isolate primary rat kidney fibroblasts and analyze oxidative levels. The mRNA and protein expression of TGF-beta 1, Col-I, alpha-SMA was investigated through quantitative PCR (qPCR), western blotting and immunohistochemistry. Antioxidant response element (ARE) motif was examined by using ARE reporter assay and chromatin immunoprecipitation. In the results, it was found that both oxidative stress and the levels of transforming growth factor beta-1 (TGF-beta 1), collagen-1 (Col-I) and alpha-smooth muscle actin (alpha-SMA) were higher in the kidneys of UUO rats than in controls. Cuiyuncao aqueous extract ameliorates renal fibrosis in rats of UUO. Furthermore, it reduces both the oxidative stress levels and the expressions of TGF-beta 1, Col-I and alpha-SMA, but in different extent in UUO rats. Upon oxidative stress, the antioxidant transcription factor NRF2 enhances the expression of numerous genes regulated by ARE. There are a few potential AREs in the upstream of Col-I and alpha-SMA respectively, but not TGF-beta 1. Among these potential AREs one of each of Col-I and alpha-SMA AREs were confirmed by functional assays. In conclusion, this study indicates that Cuiyuncao aqueous extract has a significant curative effect on renal fibrosis via antioxidant pathway. (C) 2020 Friends Science Publishers