BACKGROUND: Copper (Cu) is essential both for its role in antioxidant enzymes, like Cu/zinc (Zn) superoxide dismutase (SOD) and ceruloplasmin, as well as its role in lysyl oxidase, essential for the strength and integrity of the heart and blood vessels. With such a central role in cardiovascular health, Cu has been generally overlooked in the debate over improving our cardiovascular health. Cu deficiency has produced many of the same abnormalities present in cardiovascular disease. It seems almost certain that Cu plays a large role in the development of this killer disease, not because of its excess in the diet, but rather its deficiency. AIM: This study was undertaken to investigate the cardiovascular effects of Cu deficiency on the activity of SOD in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy. MATERIALS AND METHODS: Fifty-five patients with T2DM were recruited in this study which were divided into two subgroups based on the presence of microalbuminuria, the first group (microal buminuric group, n = 31) had a microalbuminuria between 30 and 299 μg/mg. The second group (normoal buminuric group, n = 29) had an albumin level less than 30 μg/mg. The two diabetic groups were compared to the control group (n = 37). RESULTS: The results of our study showed a significant reduction in the levels of SOD enzyme associated with an increased urinary Cu excretion in microalbuminuric group compared to the control group at P < 0.05. CONCLUSIONS: The current study illustrates that the regulation of the blood concentrations of Cu may be a potential therapeutic target for prevention and treatment of diabetic nephropathy.