This study was aimed at evaluating the metabolism of reactive astrocytes in the brains of patients with multiple sclerosis by quantitative 1-C-11 acetate positron emission tomography (PET). Magnetic resonance imaging and 1-C-11 quantitative PET were performed in eight patients with multiple sclerosis and 10 normal control subjects. The efflux rate (k2) of 1-C-11 acetate, which reportedly reflects the metabolic rate of 1-C-11 acetate, was calculated based on the one-tissue compartmental model. Fractional anisotropy was also determined to evaluate the integrity of the neuronal tracts. The values of k2 in the patients with multiple sclerosis were significantly higher than those in the normal control subjects, in both the white matter (p = 0.003) and the gray matter (p = 0.02). In addition, the white matter/gray matter ratio of k2 was significantly higher in the multiple sclerosis patients than in the normal control subjects (p = 0.02). Voxel-based statistical analysis revealed most prominent increase in k2 in the neuronal fiber tracts, as well as decrease in fractional anisotropy in them in the multiple sclerosis patients. The present study clarified that the pathological changes associated with astrocytic reactivation in multiple sclerosis patients could be visualized by quantitative 1-C-11 acetate PET.