Aims: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. Methods: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. Results: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p=0.04), geometric mean 197 mg/24 h (95% CI 114- 341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h). No changes were seen in serum creatinine, haemoglobin A1C or blood pressure. Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment (mean vitamin C 79.4 μmol/L (SD 27.8) vs. 41.9 μmol/L (18.4) and vitamin E 47.0 μmol/L (19.8) vs. 29.5 μmol/L (15.3), P<0.000001). Except for two patients that started additional blood pressure lowering treatment during the run-in period, no changes in medication, food and exercise habits or in the number of smokers occurred during the study. Conclusion: Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria. Further long-term, large-scale studies of this albuminuria reducing treatment modality are warranted.