Objective  To explore the protective effect of fosinopril (Fos) on streptozotocin (STZ) induced diabetic retinopathy(DR) mice and on the expression of angiotensin converting enzyme 2(ACE2) and vascular endothelial growth factor (VEGF) in DR mice.     Methods  Totally forty-eight healthy male Kunming mice, thirty-six were randomly selected，and a diabetic mouse model induced by STZ was constructed after 6 weeks of high-fat diet. After the successful establishment of the model, the thirty-six mice were randomly divided into three groups: model group, Fos low concentration (5 mg/kg) group, and Fos high concentration (10 mg/kg) group. The remaining twelve mice were served as the control group. After 8 weeks administration, the body weight and blood glucose level of mice in each group were determined. The change in the retinal structure was verified by HE staining. The serum level of VEGF was measured by ELISA. The expression of ACE2 in the retina tissue was verified by immunohistochemistry. The expression of ACE2 mRNA in diabetic retinopathy was analyzed by Real-time PCR. The levels of ACE2 and VEGF protein in diabetic retinopathy were detected by Western blotting.     Results  Fos (5 mg/kg, 10 mg/kg) reduced significantly the proliferation of neovascularization in the inner boundary layer, down-regulated the expression of VEGF in the serum of diabetic mice and promoted the expression of ACE2 in the retina tissue of diabetic mice. In addition, the effect of the high concentration group of Fos had a stronger effect than the lower concentration group(P＜0.05).     Conclusion  Fos has a protective effect on the retinopathy of diabetic mice. This protective effect may be mediated through the increased expression of ACE2 and the reduction of VEGF expression.