Background: High fat, high carbohydrate diets are supposedly contributing to the increased prevalence of obesity, diabetes and other metabolic disorders associated with coronary artery disease. We have examined long-term effects of a defined high fat/high fructose diet on several cardiovascular risk factors in rats. Methods: Male Sprague Dawley rats fed either regular chow (n=5) or a commercial diet containing 10% lard and 60% fructose (n=7) for 20 weeks. Plasma lipids, glucose, insulin and cytokine levels were measured. Body weight, food consumption, water consumption, and systolic blood pressure were recorded. Results: Systolic blood pressure plus serum triglycerides, total cholesterol, and insulin levels were significantly higher in the treated rats, as compared to controls. Body weight and plasma glucose levels were comparable between the groups. Conclusions: Long-term consumption of diets high in fat and fructose significantly increase several independent cardiovascular risk factors without causing obesity in rats. Longer studies warrant investigation of these changes on development of atherosclerotic lesions. Acknowledgements: Supported by NSERC, CIHR, and the Heart and Stroke Foundation.