Abstract Introduction: Hyperglycemia caused by diabetes results in oxidative stress and weakens the antioxidant defense system. Therefore, the aim of this study wasto investigate the effect of creatine supplementation with exercise on insulin sensitivity, oxidative stress indices, lipid profile and homocysteine in streptozotocin (STZ)-induced diabetic male rats Method: 40 Wistar male rats were randomly divided into four groups; control groups (Con), diabetes (Dia), diabetes+training (Dia+Tr) and diabetes+training+creatine (Dia+Tr+Cr). Diabetes was induced by injecting STZ (35 mg/kg) intraperitoneally. Swimming training was done for 12 weeks, 5 days a week for 15-50 minutes incrementally and by applying loads to the rats' tails. Rats in the supplement group received creatine supplement. Blood samples were taken to measure insulin resistance, lipid profile, oxidative and antioxidant indices and homocysteine. Results: Diabetes caused a significant decrease in body weight, insulin level, antioxidant enzymes, HDL and also a significant increase in blood glucose, glucose tolerance, lipid peroxidation, and lipid profile and homocysteine compared to the healthy control group (p< 0.05). Conclusion: In Co-administration of creatine supplementation and exercise training improve indices of oxidative stress, lipid profiles and homocysteine therefore, Creatine supplementation seems to increase the positive effects of exercise in controlling the risk factors of diabetes.
