AIM:To study the regulation mechanism of diet containing omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on retinal neovascularization in an oxygen-induced retinopathy (OIR) mouse model.METHODS:Sixty C57BL /6J mice,seven-day-old,were classified into 3 groups:A the normal control group,B the OIR model group,C the ω-3 PUFAs diet group.Each group has twenty mice and separated fed by their lactating mice.The normal control group was fed in a standard atmosphere environment,B,C groups were first fed in a hyper-oxygen atmosphere of (75 ± 2) ％ oxygen percentage for 5d,then continue fed in a standard atmosphere.The ω-3 PUFAs diet group was fed with dose base on their weight by 7.5mg/kg/d.All mice were sacrificed when they were seventeen-day-old,the relative neovascularization areas (NA) were calculated by fluorescein angiography on flat-mounted retina.The number of endothelial cell nuclei breaking through the inner linmiting membrane (ILM) was counted on hematoxylin and eosin-stained retinal section.The ω-3PUFAs/ω-6PUFAs relative amount and ratio was measured by GC-MS in the retina.A real-time PCR and Western Blot method were used to detect the mRNA,peroxisome proliferator-avtivated receptor-γ (RPAR-γ),vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR-2)in the retina.RESULTS:There was a significant different in all groups on the relative neovascularization areas and the number of endothelial cell nuclei breaking through the ILM (FNA =20.45,P＜0.05;FILM =48.66,P＜0.05).NA between Group A and B had a significant difference (t=8.64,P＜0.05),the same between Group C and B (t=8.91,P＜0.05).The cell nuclei breaking through ILM in Group A and B was significantly different (t =38.51,P＜ 0.05),the same in GroupC and B (t=19.86,P＜0.05).For the relative contain in retina of ω-3PUFAs and ω-6PUFAs,there was a significant different among all groups (F=129.86,F=112.44;all P＜0.05).That of Group C was significant different than other two groups(t=23.15,25.42;t=16.43,11.95;P＜0.05).There were significant different among all groups on ω-3PUFAs/ω-6PUFAs ratio,retinal RPAR-γmRNA expression,retinal VEGF-A mRNA expression and VEGFR-2 mRNA expression (Fω-3/6 =10.30,FRPAR-γ =138.24,FVEGF-A =69.12,FVEGFR-2 =52.45;P＜0.05).The ω-3PUFAs/ω-6PUFAs ratio of Group C was higher than that of Group B (P＜0.05).Compared to Group B,on one hand Group C had a higher expression (P＜0.05),on other hand Group C had a lower expression on VEGF-A mRNA and VEGFR-2 mRNA(P＜0.05).CONCLUSION:The diet rich with ω-3 PUFAs uplifts the ω-3PUFAs/ω-6PUFAs ratio and activates RPAR-γ to lower expression of VEGF-A and VEGFR-2 to inhabit oxygen induced retinal neovascularization.