OBJECTIVES: Elevated homocysteine levels are considered to be an independent risk factor for cardiovascular complications in diabetic patients. The aim of this study was to find out if zinc supplementation improves homocysteine levels, which may exert vascular-protective effects in type 2 diabetes subjects with microalbuminuria. METHODS: In a randomized, double-blind, controlled, crossover study, 50 type 2 diabetic patients with microalbuminuria were subdivided into two groups and supplemented with 30 mg/d of zinc (group 1) or placebo (group 2) for three months with a fourweek wash out period. Serum creatinine, vitamin B12, folate, fasting plasma glucose, HbA1c, lipid profiles, zinc, homocysteine levels and random urine albumin were measured before and after the first and second phase of the study in all participants. RESULTS: Mean serum zinc was significantly increased after zinc supplementation (from 76 ± 16 µg/dl to 93 ± 20 µg/dl; p < 0.05), while there was no change in the placebo group (75 ± 16 µg/dl to 75 ± 15 µg/dl). With zinc supplementation, homocysteine levels reduced significantly (from 13.71 ± 3.84 µmol/l to 11.79 ± 3.06 µmol/l; p < 0.05), which did not occur on placebo (from 12.59 ± 2.13 µmol/l to 13.36 ± 2.03 µmol/l). Simple regression was used to show a positive correlation between urine albumin excretion and serum homocysteine (r = 0.37, p = 0.023). Vitamin B12 and folate levels increased significantly in patients who received zinc in comparison to those who received placebo. A negative correlation was observed between homocysteine and vitamin B12 concentration (r = -0.36, p = 0.025). CONCLUSION: Zinc supplementation reduced serum homocysteine and increased vitamin B12 and folate concentrations in type 2 diabetic patients with microalbuminuria.