Retinas from male Wistar rats which were housed during a long-term drug safety study at short, medium and long distance from a fluorescent light source were examined. Retinal atrophy was pronounced in the central retina of rats housed closest to the light source, and was characterized by a loss of photoreceptor cells and of S-antigen immunoreactivity in the outer nuclear layer (ONL), absence of synaptophysin immunoreactivity in the outer plexiform layer (OPL), decrease of the number of nuclei in the inner nuclear layer (INL), astrocytic proliferation, and Müller cell activation. The peripheral retina of these rats had a laminated architecture, although the number of photoreceptor cells and nuclei in the INL was reduced. Retinas from rats housed a medium distance from the light source did not have any apparent histological or immunohistochemical changes, except for a lower number of photoreceptor cells and nuclei in the INL. The rats housed a long distance from the light source had the highest number of nuclei in the ONL and INL of the central and peripheral retina, and were used as control group. Our data indicate that retinal atrophy occurs in male Wistar rats maintained under light conditions currently used in long-term toxicity studies, and suggest that photoreceptor cell loss is followed by trans-synaptic anterograde degeneration of neurons in the INL, astrocytic proliferation and Müller cell activation.