In this chapter we summarize the commonly used animal models employed in the study of cardiovascular diseases and diabetes, two of the most prevalent oxidative stress-induced diseases. A number of animal models of atherosclerosis support the notion that reactive oxygen and nitrogen species have a causal role in atherosclerosis and other vascular diseases. Experimental atherosclerosis is induced by specific lipid-rich diets or in genetically modified strains that cause hyperlipidemia and cardiovascular diseases. Rabbits are the animals most used for the study of atherosclerosis due to their facility to generate atherosclerosis with defined fat-enriched diets. Indeed, a myocardial infarction-prone derived from Watanabe LDL receptor-deficient rabbit strain is also used. Since mice are highly resistant to atherosclerosis, only genetically modified mice, such as the knock-out mouse for apo E, LDL receptor or both, have been used. In addition, reactive species also contribute to the pathogenesis of beta-cell destruction in type 1 diabetes and beta-dysfunction on type 2 diabetes. Alloxan induces the formation of reactive oxygen species and provokes beta-cell death in type 1 and 2 diabetes mellitus, while streptozotocin involves DNA alkylation and fragmentation. Zucker rats are the most important animal models of genetic obesity and metabolic syndrome. Finally, genetically engineered diabetic models include transgenic and knock-out mice.