BACKGROUND High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. METHODS Male Sprague-Dawley rats received a HCF diet for 16 to 17weeks. Body weight was measured weekly and mean arterial blood pressure, fasting blood glucose, fasting plasma insulin, glucose tolerance, and blood lipid levels were measured following 15weeks of feeding. One to 2weeks later, while still on the HCF diet, cardiac function was examined by in vivo pressure-volume measurements in the left ventricle. Finally, protein and glucose content in the urine was measured and all organs were weighed at the end of the study. RESULTS Rats fed a HCF diet showed increased cholesterol and decreased high-density lipoprotein (HDL) levels in serum compared to control fed rats and they had more than a twofold increase in liver weight. However, in contrast to what has previously been reported, HCF diet had no effect on body weight, blood pressure, fasting blood glucose, fasting plasma insulin, glucose tolerance, or cardiac function during unstressed conditions. CONCLUSIONS We were unable to reproduce previous findings that a HCF diet causes changes in glucose tolerance and cardiac contractile performance. Therefore, further studies are warranted to evaluate specific interactions between genetic, environmental, and dietary factors on metabolic and cardiovascular disease progression associated with intake of a westernized diet.