Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for the development of atherosclerosis in humans. The development of an animal model that displays accelerated atherosclerosis associated with NIDDM will aid in elucidating the mechanisms that associate these disorders. C57BL/6 mice may provide such a model system. This strain becomes obese, hyperglycemic and insulin resistant when fed a high fat diet (diabetogenic diet) and is susceptible to atherosclerotic lesion development when fed a separate high fat diet containing cholesterol and bile acids (atherogenic diet). This report tests whether a diet commonly used to induce atherosclerosis also provokes a diabetic phenotype and whether a diet used to induce diabetes provokes the development of aortic fatty streak lesions. Mice of strains C57BL/6, C3H/He, BALB/c and seven recombinant inbred (RI) strains were fed an atherogenic diet for 14 weeks and glucose parameters were measured. No correlation was observed between atherosclerosis susceptibility and fasting insulin or glucose levels, or glucose clearance following short-term insulin or glucose treatment. Analysis of the RI strains suggested that multiple genes control these glucose metabolic parameters. Feeding the diabetogenic diet for 14 weeks to C57BL/6 mice induced obesity and diabetes and 2-fold increases in plasma lipoprotein concentrations. Also, small aortic sinus lipid deposits were observed in 40% of the mice. Thus, analysis of the diabetogenic diet fed C57BL/6 mouse may provide an important tool for further studies of diabetes accelerated vascular disease.