We investigated the influence of apolipoprotein E deficiency and Western-type diet feeding on the development and composition of neointimal lesions induced by periadventitial carotid placement of a non-occlusive collar in mice. ApoE-/- and wild-type mice were fed a Western-type diet or chow diet for 4 weeks before collar surgery. Diets were continued after collar placement for 6 or 12 weeks. Compared to sham-operated arteries, collared carotids showed significant neointima formation, lumen loss, and outward remodeling in both apoE-/- and wild-type mice. These changes were not affected by either the genotype or the diet. Conversely, significant differences in neointima composition were detected between the two genotypes, with apoE-/- mice showing greater lipid deposition and lower SMC accumulation compared to wild-type mice, independent of the dietetic regimen. Altogether, the results of the present study indicate that although lesion composition may be influenced by genotype, neointima formation and arterial remodeling in the murine perivascular carotid collar model occur independent of the exposure to atherogenic diet or the presence of a sensitized genotype such as apoE-/-. The murine perivascular carotid collar model would thus be suitable for investigating neointima formation, arterial remodeling, and their potential pharmacological modulation in the setting of different genetic and dietary conditions.