The direct effect and the interaction of diabetic angiopathy and metabolic control on free radical and antioxidant activity indices was investigated in 48 patients with type 2 diabetes mellitus. Conjugated dienes (CD) and thiobarbituric acid-reacting substances (TBARS) levels were 34 and 178% of control values, respectively. An approximate two-fold decrease in plasma thiols (PSH) and erythrocyte lysate thiols (LSH) concentrations, parameters reflecting protein oxidative damage, was found. Impairment of blood antioxidant potential in diabetic patients was reflected by an 81% increase in superoxide dismutase (SOD) activity, a 30% decrease in catalase (CT), 20% decrease in glutathione peroxidase (GPx) and glutathione reductase (GR) activities as well as by lowered total antioxidant status (TAS). CD, TBARS and SOD values were positively correlated with plasma glucose concentration and glycated hemoglobin level. A negative correlation existed between levels of LSH, PSH, CT, GPx or TAS and both glucose and HbA(1c). Blood glucose control and vascular complications had strong independent effects on prooxidant-antioxidant status, apart from blood glucose and GR activity. In addition, glycemic control and diabetic vasculopathy interact in their influence on most of the free radical and antioxidant indices, except for CD, LSH levels and CT activity. Thus, we observed different mechanisms by which vascular complications and glucose control affect blood free radical indices and antioxidant status parameters in type 2 diabetic patients.