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The objective of our study was to determine the interrelations between the "first", non-enzymatic, and the "second", enzymatic line of antioxidant defense in patients with type 2 diabetes mellitus and manifested cardiovascular complications. The second aim was to determine the relations between pro-oxidant (lipid status) and antioxidant parameters in patients under observation. Methods: In our case-control study, a total of 117 type 2 diabetic patients (69 with and 48 without cardiovascular complications) and 42 healthy subjects were included. Antioxidant enzymatic parameters: erythrocyte, Cu,Zn-SOD, glutathione peroxidase (GPx) and glutathione reductase (GR), as well as total antioxidant status (TAS), bilirubin, uric acid, total proteins, albumin and haptoglobin were determined. The enzymatic antioxidant parameters and TAS were analyzed using commercial tests manufactured by Randox Ltd. UK, based on spectrophotometer methods, while the other non-enzymatic and lipid parameters were determined by standard laboratory methods. Results: In relation to healthy subjects, type 2 diabetics with cardiovascular complications had significantly lower values of enzymatic antioxidants (P < 0.001), and higher values of total bilirubin (P = 0.050), uric acid (P < 0.001) and haptoglobin (P < 0.001). Weak positive correlation was found between SOD and GPx (R = 0.289, P = 0.028) and between SOD and GR (R = 0.259, P = 0.045), while weak negative correlation was obtained between GPx and uric acid (R = -0.35, P = 0.009), GPx and total bilirubine (R = -0.40, P = 0.018). TAS correlated weakly with triglycerides (R = 0.32, P = 0.037), while GPx and GR correlated with HDL-cholesterol (R = 0.457, P = 0.007; and R = 0.466, P = 0.001). Conclusions: Based on the obtained results, it may be concluded that type 2 diabetic patients have significantly modified antioxidant defense, with a varying degree of imbalance between the "pool" of non-enzymatic substances and the activity of enzymatic antioxidants, which depends on whether they have or not manifested cardiovascular complications. [ABSTRACT FROM AUTHOR]