Oxidative stress is the outcome of an imbalance between the production and neutralization of reactive oxygen and nitrogen species (RONS) such that the antioxidant capacity of cell is overwhelmed. The present review briefly summarized the underlying role of overwhelming levels of RONS in the pathophysiology of diabetes mellitus (DM). The primary causative factor of oxidative stress in DM is hyperglycemia, which operates via several mechanisms. However, the individual contribution of other intermediary factors to hyperoxidative stress remains undefined, in terms of the dose response relationship between hyperglycemia and overall oxidative stress in DM. Intuitively, the inhibition and/or scavenging of intracellular free radical formation provide a therapeutic strategy to prevent oxidative stress and ensuing pathologic conditions.