BACKGROUND: The main objective of the study was to analyze the potential ability of vitamins E, C, and D, used as nutritional supplements, in averting inflammation and oxidative stress in the course of diabetes mellitus. METHODS: Male mice were divided into eight groups. Diabetes was induced (groups II, VI, VII, and VIII) by an intraperitoneal injection of streptozotocin (STZ). The third and sixth groups were given vitamin C (50 mg/kg) 3 times per week, the fourth and seventh groups were given vitamin E (300 mg/kg) 3 times per week, and the fifth and eight groups were given vitamin D (2000 IU/day). Interleukin-6 levels were measured in serum. Glutathione (GSH) levels and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity were measured in the liver tissue. RESULTS: STZ resulted in a significant decrease in all tested enzymes and glutathione levels, and an increase in IL-6 level in comparison to control animals (p < 0.05). Mice treated with vitamins had a significantly (p < 0.05) higher content of enzymes and glutathione in liver than diabetic mice, however IL-6 concentration showed a significant decrease. Concurrent administration of STZ and vitamins caused a significant increase (compared to the diabetes group) in SOD, CAT, GPx, GSH content, and a decrease in IL-6 levels (p < 0.05). CONCLUSION: These results indicate the preventive role of vitamin C, E, and D against STZ-induced diabetic oxidative stress and inflammation. Hence these vitamins could be used as an adjuvant therapy for the prevention and/or management of diabetes.