Type 2 diabetes is a metabolic disease, which frequency increases substantially with age. Oxidative stress as a result of production and deactivation of free radicals unbalance, may play an important role in a complex pathogenesis of disease. Free radicals are by-products of metabolism, which in regard to their chemical structure, readily react with DNA, lipids, proteins and carbohydrates and cause changes in their structure and function. Antioxidant enzyme system and small molecule antioxidants protect organism against harmful effect of free radicals. In accordance to free radical theory of aging, antioxidant enzymes and molecules activity decrease with age. At the same time, quantity of disadvantageous changes caused by reactive oxygen species (RFT) increase. Disturbance in the prooxidant-antioxidant balance causes organism senescence and development of age-related diseases including diabetes mellitus. Hyperglycemia is an additional factor which can escalate systemic oxidative stress in diabetes mellitus. Elevated concentration of glucose increases generation of reactive oxygen species and accumulation of oxidative modified macromolecules as a result of accelerated activation of a few independent molecular pathways such as autooxidation of monosacharides, non-enzymatic glycosylation, activation of protein kinase C, phospholipase A2 and polyol pathway. Moreover aging is associated with decrease of melatonin concentration, which leads to physiological dysfunctions including depressed antioxidant defense mechanisms. Antioxidant properties of melatonin, which protects macromolecules, especially DNA, from harmful effects of RFT, are particularly important in aspect of free radical theory of aging.