Increasing evidence in both experimental and clinical studies suggests that there is a close link between hyperglycemia, oxidative stress and diabetic complications. High blood glucose level determines overproduction of reactive oxygen species (ROS) by the mitochondria electron transport chain. High reactivity of ROS determines chemical changes in virtually all cellular components, leading to DNA and protein modification and lipid peroxidation. Measurement of biomarkers such 8-hydroxy-2'deoxyguanosine (8-OHdG), isoprostanes, malondialdehyde (MDA) and nitrotyrosine is a useful tool to assess the oxidative stress of the organism. Knowledge of the mechanisms of ROS damage of is the first step for development of new therapeutic molecules and for rationalizing the use of existing drugs.