Here we show for the first time (1) retinal IGF-2 transcript levels remain high in adult rats, suggesting an active role in homeostasis; (2) basal retinal IR kinase activity depends primarily on locally generated IGF-2 rather than insulin or IGF-1; (3) diabetes reduces retinal IGF-2 mRNA content and IGF-2 protein content within vitreous fluid; and (4) intravitreal IGF-2 injection augments prosurvival IR kinase and Akt1 kinase activity in diabetic rat retinas. The gene discussed is IGF1; the disease is diabetes mellitus.