Objective: Neovascular diseases of the eye are the most common cause of blindness. Increased expression of vascular endothelial growth factor (VEGF), are the most common cause of ischemic retinopathy. Thus, understanding the pathophysiology of pathways that regulate retinal VEGF is of great interest. Estrogen-related receptor γ (ERRγ) is a constitutively active orphan nuclear receptor. It is more selectively expressed in metabolically active tissues. In the previous studies, conserved ERRγ binding site has been identified in the promoter of Vegfa gene. Thus, the authors evaluated the role of ERRγ in the retina and anti-VEGF potential of GSK5182, selective inverse agonist of ERRγ, in mouse model of retinal neovascularization. Methods: For the Oxygen-induced retinopathy (OIR) model, C57BL/6J newborn pups at postnatal day (P) 7, along with their mother, were transferred to a chamber supplied with 75 ± 1% oxygen for 5 days. On P12, the mice were returned to the room air (21% O2) and induced subsequent relative retinal hypoxia to P17. The rat retinal ganglion cell line RGC-5 cells were pretreated with GSK5182 at the indicated concentration for 1 h and were then treated with deferoxamine (DFO) for 12 h. RGC-5 cells were placed in hypoxic chamber (1% O2) or normoxic conditions. Results: Immunohistochemistry result showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17 in an OIR mouse. In a RGC-5 cell, mRNA and protein levels of ERRγ were increased by hypoxic condition. Transient transfection assay showed ERRγ directly regulated expression of Vegfa promoter and it was inhibited by GSK5182. To determine the effect of GSK5182 in vivo, GSK5182 intravitreally injected to P14 OIR mouse. GSK5182 inhibited Vegfa mRNA in P17 of the OIR model. Conclusion: Therefore, this study showed that ERRγ inverse agonist GSK5182 suppresses hypoxia-induced VEGF expression and ERRγ could be another molecular target for ischemic retinopathies.