Some of the antiglaucoma drugs have shown neuroprotective effects in ischemic retinal damage and optic nerve injury. We studied photoreceptor protection against constant light-induced damage using isopropyl unoprostone, a prostaglandin F_2α metabolite-related compound. Albino Sprague-Dawley rats were administered isopropyl unoprostone solution intravitreally in one eye (the test eye) and vehicle alone in the contralateral eye (the control eye) and were exposed to constant light for 7 days. Histological examinations were performed to evaluate photoreceptor protection by quantifying the outer nuclear layer (ONL) thickness and scoring the rescue of ONL. Seven-day constant light affected photoreceptors and produced a marked disruption of photoreceptor outer segments and inner segments and a decrease in the thickness of the ONL. As compared with control eyes, pretreatment by intravitreal administration of isopropyl unoprostone 2 days prior to constant light exposure provided protection from the light insult, and the effects of rescue were dependent on the dose of the agent (0.6–6.0 µg), the maximum dose protecting about 70% of the photoreceptors. Topical application of the drug had little rescue effect. Aberrant macrophages in light-exposed eyes with unoprostone injection were more numerous than in normal eyes, but the extent did not differ significantly from that of degenerated eyes injected with vehicle only. Isopropyl unoprostone has shown protection of photoreceptors against constant light-induced damage, and it is thus suggested that the agent has neuroprotective activity in vivo.