Abstract The effectiveness of cognitive bias modification for interpretation (CBM-I), a treatment method employed to reduce social anxiety (SA), has been examined. However, the neural correlates of CBM-I remain unclear, and we aimed to elucidate brain activities during intervention and activity changes associated with CBM-I effectiveness in a pre–post intervention comparison. Healthy participants divided into two groups (CBM, control) were scanned before, during and after intervention using functional magnetic resonance imaging. Ambiguous social situations followed by positive outcomes were repeatedly imagined by the CBM group during intervention, while half of the outcomes in the control group were negative. Whole-brain analysis revealed that activation of the somatomotor and somatosensory areas, occipital lobe, fusiform gyrus and thalamus during intervention was significantly greater in the CBM than in the control group. Furthermore, altered activities in the somatomotor and somatosensory areas, occipital lobe and posterior cingulate gyrus during interpreting ambiguous social situations showed a significant group × change in SA interaction. Our result suggests that when facing ambiguous social situations, positive imagery instilled by CBM-I is recalled, and interpretations are modified to contain social reward. These findings may help to suggest an alternative manner of enhancing CBM-I effectiveness from a cognitive-neuroscience perspective.