Our study discovered a pivotal role of the GPCR Fpr2 in promoting the pathogenesis of DR and OIR, as demonstrated by significantly ameliorated disease processes severity in mice with Fpr2 deficiency, in which the upregulation of GFAP, IBA1, and Vimentin level seen in the diseases was significantly attenuated in Fpr2−/− mice with diabetes, in association with reduced glial activation and accumulation in the retina. This evidence concerns the gene AIF1 and diabetes mellitus.