BACKGROUND The aim of the study was to examine whether biomarkers of oxidative stress are predictors of diabetic nephropathy (DN) progression. METHODS The study involved 45 patients with type 2 diabetes and DN and 15 healthy controls. Patients were followed for 3 years and the annual percentage change in eGFR was used to estimate the progression of DN. Patients with an annual percentage change in eGFR above the cutoff value of - 5.48%/year were classified in group 1, those with an annual percentage change in eGFR ≤ - 5.48%/year in group 2. RESULTS The 28 patients in group 1 had the annual percentage change in eGFR of - 4.78 and 39.12%/year, and for the 17 patients in group 2 it ranged from - 24.86 to - 6.18%/year. At the onset of the study no significant differences were found between the groups in demographic, clinical or laboratory parameters. Plasma activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly lower in patients than in the controls. During 3-year study kidney function and size changed insignificantly in group 1, while eGFR and kidney size decreased and proteinuria increased significantly in group 2. Multivariate linear regression analysis selected male gender, duration of diabetes, systolic blood pressure, fasting serum glucose, urine protein/creatinine ratio as factors associated with DN progression. Plasma activity of GPX and SOD were selected as positive predictors of annual percentage change in eGFR. CONCLUSIONS Besides already known factors, plasma activity of GPX and SOD were found to be significant independent predictors of DN progression.