Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr^-/- ApoB^100/100 (LRKOB100), and atherosclerotic/diabetic IGF-II X LDLr^-/- ApoB^100/100 (LRKOB100/IGF) mice. Each group was fed either a standard chow diet (SD), a 0.2% cholesterol diet (CD), a high fat diet (HFD) or a high fat 0.2% cholesterol diet (HFCD) for six months. The triglyceride-rich HFD increased body weight, glucose intolerance and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol however increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.