Ischemic-anoxic injury plays an important role in the pathophysiology of diabetes retinopathy, optic neuropathy, even glaucoma and other ocular diseases. It may ultimately cause damage to neuronal death like retinal ganglion cells (RGCs) and subsequent visual loss. RGCs are essential elements of the retina and optic nerve that are crucial to visual formation. Ischemic-anoxic injury, inflammation, and oxidative stress are vital causes of RGC death. Thus, neuroprotection is essential for the treatment of these ocular diseases. Recent studies have shown the neuroprotective property of apelin-13 in many disease models. In this study, we isolated RGCs and found that apelin-13 promoted the viability of RGCs and increased the phosphorylation of Protein kinase B (PKB, Akt) in an in vitro oxygen-glucose deprivation model. Moreover, apelin-13 increased the expressions of glucose-6-phosphate dehydrogenase (G6PD) and nicotinamide adenine dinucleotide phosphate (NADPH) and reduced the level of reactive oxygen species (ROS). And, we also found that apelin-13 could promote the expressions of glucose transporter-1 (GLUT1) and adenosine triphosphate (ATP). These results indicated that apelin-13 could delay or stop RGC death, which might be as potential therapeutic targets for treatment of diseases mediated by ischemic-anoxic damage like diabetes retinopathy, optic neuropathy, even glaucoma.