Recent change in lifestyle, including physical inactivity and unhealthy diets, are likely to have played an important role in global epidemic of obesity, type2 diabetes mellitus (T2DM), and the metabolic syndrome (MetS). Implementation of a healthy lifestyle, with an increase in physical activity and reduction of body weight, based on the regulation of calories and fat intake, are the basis for the prevention and treatment of lifestyle related disease. This review highlights some recent advances in the understanding of metabolic and molecular mechanisms concerning the effect of diet and focuses on the prevention and/or improvement of dyslipidemia, insulin resistance, impaired glucose homeostasis, obesity, T2DM and MetS in experimental rodent models, with some extension to humans.