Cognitive behavioral therapy (CBT), an effective treatment for depression, targets self-referential processing of emotional stimuli. We examined the effects of CBT on brain functioning during self-referential processing in depressive patients using functional magnetic resonance imaging (fMRI). Depressive patients (n = 23) and healthy participants (n = 15) underwent fMRI scans during a self-referential task using emotional trait words. The depressive patients had fMRI scans before and after completing a total of 12 weekly sessions of group CBT for depression, whereas the healthy participants underwent fMRI scans 12 weeks apart with no intervention. Before undergoing CBT, the depressive patients showed hyperactivity in the medial prefrontal cortex (MPFC) during self-referential processing of negative words. Following CBT, MPFC and ventral anterior cingulate cortex (vACC) activity during self-referential processing among depressive patients was increased for positive stimuli, whereas it was decreased for negative stimuli. Improvements in depressive symptoms were negatively correlated with vACC activity during self-referential processing of negative stimuli. These results suggest that CBT-related improvements in depressive symptoms are associated with changes in MPFC and vACC activation during self-referential processing of emotional stimuli.