Objective To establish a mouse model of renal fibrosis and hypertension induced by unilateral nephrectomy and infusion of angiotensin II using a micro-osmotic pump. Methods Thirty-six 8-week old wild type male c57BL/6 mice were randomly divided equally into three groups. The normal group was not treated, model group underwent unilateral nephrectomy and infusion of angiotensin II using a micro-osmotic pump, and the saline control group underwent unilateral nephrectomy and infusion of physiological saline using a micro-osmotic pump. Blood pressure was measured before and two and four weeks after modeling. The 24 h urine protein quantity, serum creatinine (Scr), and blood urea nitrogen (BUN) were measured, and renal pathology was examined at 4 weeks after modeling. Results At 2 weeks of the experiment, the blood pressure in the saline control group and model group was significantly higher compared with that of the normal group (P<0.05, P<0.01), and the blood pressure of the model group was significantly higher than that of the saline control group (P<0.05). Four weeks after operation, the blood pressure in the model group was still higher than that of the normal group (P<0.01) and the saline control group (P<0.05). Both the levels of Scr and BUN in the saline control group and model group were significantly higher than those of the control group (P<0.05, P<0.05). The 24 h urine protein quantity in the model group was markedly higher compared with that of the saline control group and normal group (P<0.01). The pathological examination showed that proximal tubular epithelial cells were swollen in the model group. Histology using Masson staining showed that the positive rate of collagen fibers in the model group was significantly higher than that of the normal group and saline control group (P<0.05).Conclusions Our results demonstrate that a mouse model of renal fibrosis and hypertension can be successfully established by unilateral nephrectomy and infusion of angiotensin II using a micro-osmotic pump.