Recent studies have proved in patients with type 2 diabetes the positive effects of High Intensity Interval Training (HIIT) programs on hyperglycemia and muscle mitochondrial capacity. The aim of this work was to compare the effects of HIIT with a traditional Moderate Intensity Continuous Training (MICT) on glucose metabolism and mitochondrial function in diabetic mice. 25 db/db mice aged 6 weeks were subdivided into MICT group, HIIT group, or control group (CON). Animals in the training groups ran on a treadmill 5 days/week during 10 weeks. In vivo, ex vivo and post-mortem biochemical measurements were performed at the end at the end of the protocol. HIIT lowered fasting glycemia (-40% vs CON) and HbA1c (-20% vs CON), and improved response to starch and insulin tolerance tests vs CON group. No changes were noted in MICT group regarding the glucose homeostasis. 24h respiratory exchange ratio was increased in HIIT (+6% vs CON) and MICT group (+4% vs CON) after the training program but without any changes in 24h total energy expenditure. ETC protein content was increased in HIIT vs CON, whereas other mitochondrial density markers were unchanged. Western blot analysis revealed a significant increase of muscle Glut4 content and higher Akt phosphorylation ratios only in HIIT group. This study showed that HIIT may improve glucose metabolism more efficiently than traditional MICT in diabetic mice by mechanisms independent of mitochondrial adaptations. As already reported in the literature, intact leptin signaling might be necessary for exercise-induced adaptation of mitochondrial function through AMPK and Sirt1 in the muscle