Recent neuroimaging studies have revealed that acupuncture stimulation modulates human central nervous system including cerebral limbic/paralimbic and subcortical structures. Due to the wide and intricate connections with cerebrum, we hypothesized that anatomically specific areas in human cerebellum are also modulated by acupuncture stimulation beyond classical involvement of cerebellum in motor coordination. Functional MRI (fMRI) was used to investigate neural substrates responding to the acupuncture stimulation of Pericardium 6 (PC6, Neiguan), an acupoint relevant for the management of nausea including vestibular-related motion sickness. Sham stimulation near the acupoint and tactile stimulation on the skin of the acupoint were given as separate conditions. Psychophysical scores as well as the heart and respiratory rates were measured during each condition. Acupuncture manipulation on PC6, in comparison to the sham acupuncture and tactile stimulation conditions, selectively activated left superior frontal gyrus, anterior cingulate gyrus, and dorsomedial nucleus of thalamus. Acupuncture-specific neural substrates in cerebellum were also evident in declive, nodulus, and uvula of vermis, quadrangular lobule, cerebellar tonsil, and superior semilunar lobule. Negative MR signal changes, often seen during the acupuncture of analgesic points, were not observed in the present study. Our data suggest that cerebellum serves as important activation loci during the acupuncture stimulation of PC6, and clinical efficacy of PC6 may be mediated by the cerebellar vestibular neuromatrix.