Abstract： Objective To explore the central mechanism of acupuncture in regulating immune function by composite analysis of immune-related indexes in peripheral blood and functional MRI (fMRI) signal changes after acupuncturing Zusanli (ST36) acupoint. Methods Thirteen healthy adult volunteers were divided into the true acupoint group (n=13) and the false acupoint group (n=8, who also participated in the true acupoint group). The true accupoint group used the Zusanli acupoint. Peripheral blood was drawn 5 min before the needling and 30 min after removing the needling for detection of the immune-related indexes. The fMRI was performed during acupuncture, and fMRI data obtained were analyzed by SPM2 software. Results The numbers of CD4, CD4/CD8 and NK cells after acupuncture increased significantly as compared with those before the needling in the true acupoint group (P<0.05), while no significant changes were noted in the false acupoint group (P>0.05). The fMRI showed that acupuncture on the Zusanli activated the left hypothalamus, bilateral head of the caudate nucleus, anterior cingulate cortex, posterior cingulate cortex, paracentral lobule, middle temporal gyrus, middle frontal gyms and cerebellar hemisphere; acupuncturing the false acupoint only activated the paracentral lobule and cerebellar hemisphere. Conclusion The regulatory action of acupuncturing the Zusanli acupoint on immune function is closely related to the Center-specific brain regions.