Abstract.[Purpose] The purpose of this study was to investigate the neural mechanisms of the brain regions activated by training dependent changes in large-scale motor networks induced by performance of sequential motor learning, using functional MRI.[Method] Twenty healthy subjects were recruited, who were randomly allocated to the training or control group. The training group performed a serial reaction time task for two weeks, whereas the control group did not receive any training. Behavioral assessment was conducted in terms of response accuracy and reaction time during pre-and post-fMRI scanning.[Results] The training group showed a significant improvement in motor performance. On the other hand, the control group also showed a slight improvement of performance. After the two-week training, activations of all areas observed on the initial fMRI showed a remarkable decrease, whereas no differences or slight increases were observed in the change of activation in the control group. In the cerebellar activation of the training group, the most prominent change was observed in the medial cerebellar area, and contralateral deep cerebellar nuclei were newly activated.[Conclusion] Our findings suggest that brain reorganization for sequential motor learning was induced by motor sequence acquisition, and that decreased cerebral and increased cerebellar activity during explicit learning might be related to familiarity with the task.