The aim of this study was to observe the grey matter (GM) tissue changes of ischemic stroke patients, to explore the therapy responses and possible mechanism of acupuncture. 21 stroke patients were randomly assigned to receive either acupuncture plus conventional (Group A) or only conventional (Group B) treatments for 4 weeks. All patients in both groups accepted resting-state functional magnetic resonance (fMRI) scan before and after treatment, and the voxel-based morphometry (VBM) analysis was performed to detect the cerebral grey structure changes. The modified Barthel index (MBI) was used to evaluate the therapeutic effect. Compared with the patients in Group B, the patients in Group A exhibited a more significant enhancement of the changes degree of MBI from pre- to post-treatment intervention. VBM analyses found that after treatment the patients in Group A showed extensive changes in GMV. In Group A, the left frontal lobe, precentral gyrus, superior parietal gyrus, anterior cingulate cortex, and middle temporal gyrus significantly increased, and the right frontal gyrus, inferior parietal gyrus, and middle cingulate cortex decreased (P < 0.05, corrected). In addition, left anterior cingulate cortex and left middle temporal gyrus are positively related to the increase in MBI score (P < 0.05, corrected). In Group B, right precentral gyrus and right inferior frontal gyrus increased (P < 0.05, corrected). In conclusion, acupuncture can evoke pronounced structural reorganization in the frontal areas and the network of DMN areas, which may be the potential therapy target and the potential mechanism where acupuncture improved the motor and cognition recovery.