Carotenoids are believed to inhibit oxidative stress. We investigated the protective effect of lutein and egg yolk supplementation on systemic and retinal alterations in apolipoprotein E-deficient (apoE-/-) mice, an experimental model of hypercholesterolemia and cardiovascular disease. Three-month-old wild-type and apoE-/- mice received one of the following: vehicle, lutein (0.09 mg/kg per day) or egg yolk (0.8 g/kg per day), by gastroesophageal cannula for 3 months. Total cholesterol (TC), triacylglycerol (TG) and lipid peroxidation (TBARS) were measured in plasma. TBARS levels were also determined in retinal homogenates. Ultrastructural morphology was analyzed by electron microscopy. ApoE-/- mice, with increased TC and TG concentrations, had higher systemic (P<.05) and retinal (P<.01) levels of lipid peroxidation than wild-type strains. Electron microscopy showed ultrastructural alterations (basal laminar deposits, open intercellular junctions, increased cytoplasmic vacuoles) in the retinas from apoE-/- mice. Egg yolk significantly reduced plasma TG (P<.05) and, without changes in TC, decreased plasma lipid peroxidation (P<.05). Lutein supplementation marginally affected the parameters. Less severe retinal ultrastructural alterations were observed in apoE-/- mice receiving either egg yolk or lutein. In the apoE-/- mouse model, egg yolk improved the lipid profile and reduced systemic lipid peroxidation (P<.05). While lutein and egg yolk did not seem to reduce retinal lipid peroxidation, a reduction in retinal ultrastructural alterations was observed.