AIM: To investigate the effect of gold nanoparticles on retinal angiogenesis in vitro and in vivo, and to reveal the possible mechanism. METHODS: Seed growth method was used to synthesize gold nanoparticles (GNPs). The size, zeta potential, absorption spectrum and morphology of GNPs were identified using Malvern Nano-ZS, multimode reader (BioTek synergy2) and transmission electron microscope. Cell viability was analyzed using cell counting kit-8 method and cell growth was assessed with EdU kit. Transwell chamber was used to investigate cell migration. Tube formation method was used to assess the angiogenic property in vitro. Oxygen induced retinopathy (OIR) model was used to investigate the effect of GNPs on retinal angiogenesis. Confocal microscope and Western blot were used to study the possible mechanism of GNPs inhibited angiogenesis. RESULTS: The GNPs synthesized were uniform and well dispersed. GNPs of 10 μg/mL and 20 μg/mL were able to inhibit human umbilical vein endothelial cells proliferation (50% and 72% separately, P<0.001), migration (54% and 83% separately, P<0.001) and tube formation (52% and 90% separately, P<0.001). Further data showed that GNPs were able to improve the retinopathy in an OIR model. The possible mechanism might be that GNPs were able to induce autophagy significantly (P<0.05). CONCLUSION: The present study suggests that GNPs are able to inhibit retinal neovascularization in vitro and in vivo. GNPs might be a potential nanomedicine for the treatment of retinal angiogenesis.