Background Oxidative stress forms the foundation for the induction of multiple cellular pathways which can lead to the complications of diabetes mellitus that the most debilitating ones are diseases of the nervous system. In this study, we evaluated whether treadmill running could alleviate oxidative stress and apoptosis rate in the hippocampus of streptozotocin- induced diabetic rats. Methods Forty male Wistar rats were randomly divided into four groups (n=10): Control group (CR), exercised group (CE), diabetic group (DR) and diabetic-exercised group (DE). Diabetes was induced by injection of streptozotocin in male rats. All rats in the trained group run on a rodent motor-driven treadmill for eight weeks. At the end of eight weeks, hippocampi of animals were immediately removed on ice and kept frozen. The light supernatant was taken and stored at -80°C. They were used for determination of antioxidant enzymes and TBARs level. Index of apoptosis was detected by cell death detection ELISA Kit. Results Levels of TBARs in DR and DE groups were significantly higher than CR group. SOD and GPx activities significantly increased in CE group and decreased in DR group. CAT activity significantly decreased in DR group versus CR group. The apoptosis rate significantly increased and decreased in DR and CE groups respectively compared to CR. Conclusion Exercise had beneficial effects in the diabetic exercised rats, possibly in part because of alterations in the ability to adapt to exercise-induced oxidative stress.