Background: Hyperglycaemia-induced progression of brain and erythrocyte oxidative injuries might be modulated by melatonin and selenium as potent antioxidants. The present study was conducted to explore whether melatonin and selenium protect against diabetic brain and erythrocyte oxidative stress levels in streptozotocin (STZ)-induced diabetic rats.Materials and methods: Seventy rats were equally divided into seven groups. The first and second groups were used as untreated and placebo treated controls. The third group was treated with STZ to induce diabetes. The fourth and sixth groups received 10mgkg(-1) melatonin. The fifth and seventh groups were treated with 1.5mgkg(-1) selenium (sodium selenite). The sixth and seventh groups were treated with STZ administered with melatonin and selenium as described for the fourth and fifth groups.Results: Brain and erythrocyte lipid peroxidation levels and plasma IL-1 and IL-4 levels were high in the STZ group, although they were low in melatonin and selenium treatments. Decreased glutathione peroxidase, reduced glutathione, total antioxidant status, vitamins A and vitamin E values in brain and erythrocyte of STZ group were increased by melatonin and selenium treatments.Discussion: Melatonin and selenium induced protective effects against diabetes-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production.