Objectives: Oxidative stress can contribute to microvascular complications in diabetes. A decisive event associated with this condition may be the decrease in the synthesis of zinc-containing antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. This consideration led us to investigate the effect of zinc supplementation versus placebo on microalbuminuria in diabetic patients in a randomized double blind clinical trial. Methods: Fifty diabetic patients with microalbuminuria were enrolled. Fasting plasma glucose, HbA1c, lipid profiles, plasma zinc levels and random urine for albumin and creatinine were measured. Patients randomly received 30 mg elemental zinc (group 1) or placebo (group 2) for 3 months. After a 4 week wash-out period, the groups were crossed over (i.e. the zinc group were given placebo, and the placebo group were given zinc) and the protocol was repeated. Results: From an initial number of 50 selected patients (25 in each of two groups), 39 patients (21 in group 1 and 18 in group 2) completed the study. In group 1, after zinc supplementation, urinary albumin excretion decreased significantly from 86.5 ± 57 to 75 ± 71 mg/g (p = 0.01). After placebo, patients in group 1 showed no significant reduction in microalbuminuria (85 ± 72 mg/g to 83 ± 63 mg/g creatinine). In group 2, no change in albumin excretion was observed after placebo treatment (90.5 ± 63 mg/g to 90 ± 60 mg/g creatinine). After zinc supplementation, a significant reduction was observed in albumin excretion, from 90 ± 60 mg/g to 85 ± 57 mg/g creatinine (p = 0.003). Conclusion: Zinc supplementation reduced albumin excretion in microalbuminuric type 2 diabetic patients. This outcome may be due to the antioxidant effect of zinc.