Abstract: Objective To observe the effect of febuxostat on renal tubular phenotypic transformation in hyperuricemia rats. Methods Thirty-six male Sprague-Dawley (SD) rats were randomly divided into three groups: control group, model group and febuxostat group, with 12 rats in each group. The oteracil potassium was used to induce hyperuricemia by gastric gavage. Model group received oteracil potassium once a day, and for rats in febuxostat group, additional febuxostat was administered at the same time, and control group received the same concentration of saline without oteracil potassium. The content of serum uric acid (UA), serum creatinine (Scr) and blood urea nitrogen (BUN) were measured at week 0, 4 and 8. The rats were sacrificed at the end of the experiment. Renal pathological changes were observed via HE staining and Masson staining, and the expression of α-SMA and E-cadherin in renal were detected by immunohistochemistry. Results At the end of the 8th week, the levels of serum UA, Scr, BUN and the expression of α-SMA in model group were higher than those in control group (allP＜ 0.01) coupled with significant reduction of E-cadherin (P＜ 0.01); Compared with model group, the value of serum indexes and the expression of α-SMA in febuxostat group decreased obviously, and the differences were statistically significant (allP＜ 0.01) with significant increase of E-cadherin (P＜ 0.01) and decrease of area of tubular interstitial fibrosis (TIF) (P＜ 0.01). Conclusion Hyperuricemia may cause renal tubular cell phenotypic transformation in rats and promote early renal fibrosis. Febuxostat treatment can reduce the uric acid level and ameliorate renal damage in hyperuricemia rats.