Objective To compare the effects of different doses of adenine (ADE) by oral gavage in a mouse model of renal fibrosis (RF), and to provide a more suitable mouse model for further RF research. Methods Thirty C57BL / 6J Nifdc mice were divided randomly into a control group, low-dose ADE group (ADE-L group, 50 mg / kg),and high-dose ADE group ( ADE-H group, 100 mg / kg), and the general condition, mortality, and body mass changes of the mice were observed. Serum creatinine (CREA), blood urea nitrogen (BUN), and uric acid (UA) were measured on day 30 to evaluate renal function. Histopathological changes in kidney tissues were observed by hematoxylin-eosin (HE) and Masson staining, and expression levels of fibronectin (FN), collagen Ⅰ (COL Ⅰ),and alpha smooth muscle actin (α-SMA) in kidney tissues were detected by Western Blot. Results The cumulative mortality rates in the ADE-L and ADE-H groups were 91. 7% and 58. 3%, respectively. The body mass of mice in the ADE-L group was similar to that in the control group (P>0. 05), but the body mass of mice in the ADE-H group was significantly lower than that of mice in the control and ADE-L groups from day 3 to day 30 (P<0. 001). Day 30 CREA and BUN levels in the ADE-L group were similar to those in the blank group, but CREA and BUN levels were significantly increased in the ADE-H group (P<0. 001). There were no significant differences in UA levels among all groups. Inflammatory infiltration and tubular dilatation were observed in the ADE-L group on day 30, accompanied by tubular epithelial necrosis, while crystal accumulation in the tubular lumen and interstitium was observed in the ADE-H group, and the degree of interstitial fibrosis was significantly higher than in the control group (P<0. 01).Expression levels of interstitial fibrosis-related proteins in the ADE-H group on day 30 were significantly higher than in the control and ADE-L groups (P<0. 05, P<0. 01 or P<0. 001). Conclusions Both 50 and 100 mg / kg of ADE can be used to establish a mouse model of RF, with different doses leading to varying degrees of renal injury. Mice in the ADE-L group developed mild interstitial fibrosis on day 30, while mice in the ADE-H group developed moderate to severe interstitial fibrosis.