The present study shows that feeding rats diets high in either dietary fat or dietary fructose results in distinctly different hepatic, metabolic and inflammatory profiles in rats. When comparing the effect of dietary fat and fructose, high-fat feeding more potently induce development of fatty liver and associated hepatic inflammation without affecting the circulating lipid pool. In contrast, high-fructose feeding appear to have the most pronounced effects on the plasma lipid profile, while only subtle effects on the liver are observed. The combination of fat, fructose, and cholesterol exacerbated and intensified overall effects on the liver. The strength of this study is the direct comparison of dietary fat (with very restricted amounts of carbohydrate) and dietary fructose (with very restricted amounts of fat) on parameters associated with NAFLD. This enables a more detailed evaluation of the individual roles of these macronutrients in disease progression. Furthermore, the use of qCT allows the non-invasive assessment of NAFLD-progression throughout the study, a method which to our knowledge has not previously been applied in rat studies comparing NAFLD progression after administration of different diets.