Urethane injection in newborn rats causes a photoreceptor degeneration without initial damage to the retinal pigment epithelium, choriocapillaris, or inner retina. In later stages, retinal vessels become incorporated into the retinal pigment epithelium (RPE) and change from a continuous endothelial cell phenotype to a fenestrated phenotype. At the light-microscopic level, there do not appear to be morphologic changes in the inner retina up to 24 weeks of age. Ultrastructurally, however, there are alterations in Müller cell cytotopographic organization. In the normal retina, intermediate filaments are primarily found from the ganglion cell layer to the inner nuclear layer. These filaments do not show glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the normal animal. In the urethane-treated animals, the compartmental organization of the Müller cell organelles is moved vitread. Intermediate filaments are found in the end-foot region, and in the inner plexiform layer, bundles of intermediate filaments become more prominent. All of these filaments are GFAP-IR positive. The new expression of GFAP in the Müller cell may be linked to the observed rearrangement of the cytoskeletal elements. In urethane-induced retinopathy, GFAP-IR is found associated with vessels in all layers of the remaining retina. However, it is not seen accompanying vessels into the RPE. Ultrastructurally, there is no glial investment of the RPE-associated vessels. This absence of glial investment may permit the change in phenotype observed in these vessels.