A number of randomized trials suggest that glycemic control in the initial stages decreases the macro vascular outcome and complications such as retinopathy, nephropathy and neuropathy due to micro vascular changes. Epidemiological studies indicate that memory effect continues and complications develop even after return to normoglycemia in hyperglycemic diabetic patients. Metabolic abnormalities that occur during diabetes stimulate the production of reactive oxygen species in mitochondria and hyperglycemic memory initiates a vicious cycle of ROS induced mutations in mitochondrial DNA. Interaction of advanced glycation end products (AGEs) with its receptor (RAGE) has played an important role in the pathogenesis of diabetes and its complications. AGEs upregulate RAGE mRNA levels by promoting intracellular ROS (reactive oxygen species) generation. Hence, to overcome the long term complications which develop due to hyperglycemia, therapeutic interventions to reduce the formation of oxygen radicals and block the formation of advanced glycation end products is crucial.