Pituitary adenylate cyclase activating popypeptide (PACAP) is a pleiotropic neuropeptide, exerting neurotrophic and neuroprotective effects in numerous models of in vitro and in vivo nervous injuries. The aim of the present study was to investigate whether PACAP is neuroprotective in ischemic retinal damage. Adult male Wistar rats underwent bilateral carotid occlusion and PACAP was administered unilaterally into the vitreous body immediately following carotid occlusion. Retinas were analyzed three weeks after the injury. It was found that bilateral carotid occlusion led to a severe degeneration of all retinal layers. PACAP treatment significantly ameliorated the carotid occlusion-induced retinal damage: the overall thickness of the retina was significantly more than in control carotid occluded animals and the morphological characteristics of the photoreceptors showed nearly normal appearance. The outer plexiform layer remained discernible and the inner and outer nuclear layers were significantly thicker than in control animals. In summary, our present study provides evidence, for the first time, that PACAP attenuates ischemic retinal degeneration.