The creation of mouse models that recapitulate human diabetic cardiovascular disease remains a significant challenge. Part of the problem relates to the lack of a clear understanding of the human phenotype. Although improved insulin- treat of hyperglycemia reduces cardiovascular events in patients with type 1 diabetes, similar data are not available in type 2 diabetes. Moreover, whether human vascular disease is increased by hyperglycemia, defective insulin actions, or other factors is not known. Significant progress has been made in developing models of both type 1 and type 2 diabetes in mouse that can be used to study the relationship between hyperglycemia and atherosclerosis. This review describes mouse models that recapitulate specific aspects of diabetic dyslipidemia, hyperglycemia/insulin resistance, and diabetic vascular disease. Overall, the studies have clearly demonstrated that hyperlipidemia is a major driver of atherosclerotic vascular disease in the mouse. The effects of hyperglycemia and insulin resistance on murine atherosclerosis remain uncertain.