ObjectiveTo explore the inhibition effect of Cysteine-rich 61(CCN1;Cyr61) specific siRNA expression vector on RNV in a mouse model of oxygen-induced retinopathy (OIR). MethodsOne hundred and twenty healthy C57BL/6J mice were chosen and randomly divided into the experimental group and control group, with 60 mice in each group. The experimental group was intravitreously injected with CCN1siRNA recombinant plasmids. The control group was injected with vector plasmids. Adenosine diphosphate-ase stained retina flat-mounts was performed to assess the retinal vascular profiles, retinal section with HE staining was applied to count the number of new vascular cell nuclei and the protein and mRNA expression of CCN1 and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry, Western blot and Real-time RT-PCR. ResultsCompared with control group, regular distributions, good branches and reduced density of retinal neovascularization were observed in the experimental group. The number of nucleus of vascular endothelial cells breaking through the inner limiting membrane was obviously less in the experimental group than that in the control group (t=8.756, P < 0.05). The expression of CCN1 and VEGF were obviously decreased in the experimental group compared with the control group (all P < 0.05). ConclusionThe development of RNV of ROP can be markedly inhibited by RNA interference targeting CCN1, and CCN1siRNA may provide an effective method for preventing vascular proliferative retinopathy.