Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of blindness in industrialized countries. Oxidative stress plays an important role in the development of microangiopathic complications in diabetes. Manganese superoxide dismutase (MnSOD) is a key mitochondrial antioxidant enzyme in the cellular defense against agents that induce oxidative stress. The aim of the present study was to assess whether the MnSOD A16V (C47T) polymorphism is associated with Diabetic retinopathy in northern Iran. 140 patients with Diabetic retinopathy and 140 healthy individuals, aged 30 to 75 years old, participated in this study. For genotyping of the MnSOD A16V polymorphism the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used. The prevalence of genotype frequencies AA, AV, VV in Diabetic retinopathy subjects were 5.71, 71.43 and 22.86%, respectively, while in controls they were 21.43, 38.57 and 40%, respectively. A significantly increased frequency of the AV genotype was observed in patients as compared with controls (OR = 6.94, 95% CI = 2.98-16.20, P < 0.0001). In conclusion, it is suggested that the MnSOD A16V polymorphism may be associated with the risk of Diabetic retinopathy in northern Iran. However, larger population-based studies are needed for clarifying the relation between Diabetic retinopathy and the MnSOD A16V polymorphism.