Objective To compare the effects of different doses of adenine (adenine, ADE) oral gavage on a mouse model of renal fibrosis (Renal fibrosis, RF), and to provide a more suitable mouse model for further RF research. Methods Thirty C57BL/6J mice were randomly divided into a blank group, a low-dose ADE group (ADE-L group, 50 mg/kg), and a high-dose ADE group (ADE-H group, 100 mg/kg). After modeling, the general condition, mortality, and body weight changes of the mice were observed. On day 30, serum creatinine (CREA), blood urea nitrogen (BUN), and uric acid (UA) were measured to evaluate renal function. Histopathological changes in kidney tissues were observed using HE and MASSON staining, and the expression of fibronectin (FN), collagen I (COL I), and alpha smooth muscle actin (α-SMA) in kidney tissues was 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 weight of the ADE-L group was not significantly different from that of the blank group (P > 0.05). The body weight of the ADE-H group was significantly lower than that of the blank group and the ADE-L group from day 3 to day 30 (P < 0.01). On day 30, compared with the blank group, the renal function indicators CREA and BUN in the ADE-L group showed no significant differences, while the CREA and BUN levels in the ADE-H group were significantly increased (P < 0.01). There were no significant differences in UA levels among all groups. In the ADE-L group, inflammatory infiltration and tubular dilatation were observed on day 30, accompanied by tubular epithelial necrosis. In the ADE-H group, significant crystal accumulation in the tubular lumen and interstitium was observed, and the degree of interstitial fibrosis was significantly higher than that in the blank group (P < 0.01). On day 30, the expression of interstitial fibrosis-related proteins in the ADE-H group was significantly higher than that in the blank group and the ADE-L group (P < 0.01). Conclusion Both 50 mg/kg and 100 mg/kg of ADE can successfully prepare a mouse model of RF, and different doses of adenine induction can lead to varying degrees of renal injury. The ADE-L group develops mild interstitial fibrosis on day 30, while the ADE-H group develops moderate to severe interstitial fibrosis.