Objective To examine the values of Regional Homogeneity (ReHo) in first-episode, treatment-naive patients with major depressive disorder before and after antidepressant treatment in order to explore the neural mechanism of antidepressants. Methods Twenty-five first-episode, treatment-naive patients with major depressive disorder, which met with DSM-IV diagnosis criteria underwent fMRI resting-state scans before and after 8-week antidepressant treat-ment. Paired Samples T-test was used to analysis the differences between two groups. Results The ReHo in the patient group after treatment were significantly decreased in the right medial frontal gyrus, left inferior parietal lobule, left middle temporal gyrus, left insula, right precuneus, left cingulate gyrus and posterior lobe of the cerebellum , while significantly in-creased in the right medial frontal gyrus, left medial frontal gyrus, right inferior parietal lobule, left postcentral gyrus and right middle temporal gyrus compared with before treatment. Conclusions E xtensive abnormal activity within the default mode network in the resting-state may be involved in the neuropathophylogical substrate of depression and the abnormal activity can be partly reversed by antidepressant treatment, suggesting that regional homogeneity can be used to dynamical-ly evaluate the effect of antidepressant treatment.