More evidence shows that the brain energy demands are enormous. This study aimed to examine the metabolism changes in the brain of hypoxic ischemic encephalopathy (HIE) mice model and to evaluate how treadmill exercise enhances brain metabolism. We used unilateral carotid common artery ligation mice model to simulate the clinical HIE patients. Several behavior tests were used to evaluate the motor and cognitive function impairment, western blot and immunofluorescence were used to assess the metabolism related protein changes in the different groups. Meanwhile, the HIE mice models were randomly divided into exercise training group (HIE-T) which were subjected to four weeks of treadmill exercise training and non-exercise training group (HIE-NT). The results revealed that there was decreased expression of glucose transporters GLUTs in HIE and an enhanced expression of monocarboxylate transporters MCTs, which is an important part of energy metabolism adaptation. After the period of treadmill exercise training, the expression of GLUT1 as well as MCT1 increased in the motor cortex of HIE mice model. Moreover, the mitochondrial cristae and edges were clear and intact under Transmission electron microscope compared with HIE-NT group. This suggests that increased brain energy attributed to treadmill exercise training shows promising therapeutic potential for HIE.