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Chronic hyperglycemia statue noticed in diabetes mellitus favors the manifestation of oxidative stress by increasing the production of reactive oxygen species and/or by reducing the antioxidant defense system activity. Zinc plays an important role in antioxidant defense in type 2 diabetic patients by notably acting as a cofactor of the superoxide dismutase enzyme, by modulating the glutathione metabolism and metallothionein expression, by competing with iron and copper in the cell membrane and by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase enzyme. Zinc also improves the oxidative stress in these patients by reducing chronic hyperglycemia. It indeed promotes phosphorylation of insulin receptors by enhancing transport of glucose into cells. However, several studies reveal changes in zinc metabolism in individuals with type 2 diabetes mellitus and controversies remain regarding the effect of zinc supplementation in the improvement of oxidative stress in these patients. Faced with the serious challenge of the metabolic disorders related to oxidative stress in diabetes along with the importance of antioxidant nutrients in the control of this disease, new studies may contribute to improve our understanding of the role played by zinc against oxidative stress and its connection with type 2 diabetes mellitus prognosis. This could serve as a prelude to the development of prevention strategies and treatment of disorders associated with this chronic disease.