Diabetes mellitus is associated with hyperglycemia, hyperlipoproteinaemia and oxidative stress at cellular level. The aim of the present study was to determine the relationship between anti-oxidative system of cells and hyperglycemia induced reactive oxygen species (ROS) in type-1 and type-2 diabetic patients with and without nephropathy. ROS are anihilated by an intracellular enzymatic system such as glutathione peroxidase (GPx) and catalase and the reduced glutathione (GSH) is the major antioxidant of erythrocytes and plasma. Total of 200 diabetic patients and 50 of normal healthy control individuals were recruited for the present study. Erythrocytes and plasma activities of GPx, catalase and GSH were measured as a part of anti-oxidative system and TBARS for the marker of oxidative stress in type-1 diabetes mellitus (T1DM), type-2 diabetic mellitus (T2DM), type-1 diabetes with nephropathy (T1DN) and type-2 diabetes with nephropathy (T2DN) patients. GPx, catalase and GSH activity was significantly decreased, whereas TBARS level was significantly increased in both type-1 and type-2 diabetic groups with and without nephropathy than the normal healthy individuals. T1DM patients had shown decreased level of GSH and activity of anti-oxidative enzymes than T2 DM patients, whereas TBARS level was higher in T1DM than T2DM patients, suggesting that T1DM patients are more prone to secondary complications such as nephropathy than T2DM patients. Obtained results have shown positive correlation of GSH with GPx and catalase activity in erythrocytes and plasma, whereas, negative correlation was observed between TBARS and catalase in erythrocytes and plasma indicative of the relationship of various anti-oxidative enzymes and key antioxidant such as GSH in erythrocytes and plasma responsible for increased oxidative stress.