AIM: To study the inhibitory effect of captopril on retinal neovascularization (RNV). METHODS: Sixty seven-day-old mice were randomly divided into treated group and control group with thirty mice in each group. These mice were exposed to 750 ± 50mL/L oxygen for 5 days and then to room air. The treated group had been injected captopril (2.7mL/kg), while control group had been injected 9g/L sodium chloride (2.7mL/kg) by intravitreal for 5 days. The mice were sacrificed at the 17th day after birth and the eyes were enucleated. Adenosine diphosphate-ase (ADPase) stained retina flat-mounts was performed to assess the retinal vascular profiles, Hematoxylin Eosin (HE) staining method was applied to count the number of new vascular cell nuclei and the expression of matrix metalloproteinase-2 (MMP-2) and pigment epithelium derived factor (PEDF) was detected by immunohistochemical method. · RESULTS: Comparing with control group, regular distributions, good branch and reduced density of RNV were observed in the treated group. The number of nucleus of new vessels vascular endothelial cells breaking through the internal limiting membrane was less in the treated group than in the control group ( <0.05). Stain of retinal MMP-2 was weaker in the treated group than in the control group and stain of retinal PEDF was stronger in the treated group than in the control group. CONCLUSION: Intravitreal injection of captopril (2.7mL/kg) may block the RNV in the oxygen-induced mouse model and the method may provide an effective method for preventing RNV.