Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate the shortfall caused by reduced fatty acid oxidation. Short-term moderate altitude exposure plus endurance physical activity has been found to improve glucose tolerance (not fasting glucose) in humans, which is associated with the improvement in the whole-body insulin sensitivity. However, most of people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness and insulin resistance. There is a wide variation among individuals in response to the altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity was not apparent in those individuals with low baseline dehydroepiandrosterone sulfate (DHEA-S) concentration. In rats, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can also improve insulin sensitivity, secondary to an effective suppression of adiposity. After prolonged hypoxia training, obese abnormality in upregulated baseline levels of AMP-activated protein kinase (AMPK) and AS160 phosphorylation in skeletal muscle can be reversed. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on the favorable change in body composition. Conclusion: Altitude training can exert strong impact on our metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting metabolic syndromes.