Increasing evidences have suggested that oxidative stress plays a major role in the pathogenesis of diabetes mellitus (DM). Oxidative stress also appears to be the pathogenic factor in underlying diabetic complications. Reactive oxygen species (ROS) are generated by environmental factors, such as ionizing radiation and chemical carcinogens, and also by endogenous processes, including energy metabolism in mitochondria. ROS produced either endogenously or exogenously can attack lipids, proteins and nucleic acids simultaneously in living cells. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might promote the development of DM complication and cause pancreatic beta cell damage. However, all these pathways have in common the formation of ROS, that, in excess and over time, causes chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. Various methods for determining biomarkers of cellular oxidative stress have been developed, and some have been proposed for sensitive assessment of antioxidant defense and oxidative damage in diabetes and its complications. However, their clinical utility is limited by less than optimal standardization techniques and the lack of sufficient large-sized, multi-marker prospective trials.