The purpose of this study was to ascertain whether the excess of cholesterol in rabbits induces ultrastructural retinal changes similar to those observed in human age-related macular degeneration (AMD). New Zealand rabbits were divided into two groups: Control (GO; n = 10), fed standard diet for 8 months; hypercholesterolemic (G1; n = 10), fed with 0.5% cholesterol-enriched diet for 8 months. Eyes were processed for transmission electron microscopy (TEM) and immunohistochemistry (anti-glial fibrillary acidic protein, GPAP). In comparison with GO, G1 exhibited alterations in all the retinal layers that were more intense in areas overlying altered retinal pigment epithelium (RPE). RPE changes showed no preferential location. In G1, Bruch's membrane was thicker as a result particle build-up in the collagen layers; the cytoplasm of RPE showed dense bodies, debris from cell membranes, vacuoles and numerous clumps of lipids; necrosis and apoptosis were detected in different retinal layers; Müller cells and astrocytes were reactive with instances of apoptosis and necrosis; some Müller cells filled up the empty spaces left by degenerated neurons in all retinal layers; some Müller cell nuclei were displaced to the nerve-fiber layer (NFL); epiretinal perivascular astrocytes contained drops of lipids; the NFL had very few astrocytes and the basal membranes of capillaries in the NFL was thicker. Excess cholesterol induces ultrastructural changes in the rabbit retina similar to those in human AMD. Given that lipid intake is most dependent on food composition, dietary regimen could help induce or prevent retinal disease.