Objective To investigate the effect of inducible nitric oxide synth ase (iNOS) or cyclooxygenase－2 (COX－2) on retinal neovascularization and its possible mechanism in oxygen－induced retinopathy （OIR） mouse model. Methods Retinal neovascularization was induced by oxygen with different concentration. The expression of iNOS, COX－2, matrix metalloproteinases 2 (MMP－2) and vascular end othelial growth factor (VEGF) in the retinae of experimental animals were analyzed by immunohistochemistry, realtime polymerase chain reaction and western blotting technologies. Results The inhibition of COX－2 or iNOS obviously attenuated retinal neovascularization and decreased the expression of VEGF and MMP－2. The iNOS inhibition decreased COX－2 expression, and vice versa. Conclusions COX－2 and iNOS may play a role in retinal neovascularization in OIR mouse model, which may act by regulating the expression of VEGF and MMP－2.