Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, in which the release of reactive oxygen species by infiltrating immune cells contributes to demyelination. American ginseng ( Panax quinquefolius ) is a natural health product with numerous beneficial properties, including anti-inflammatory and anti-oxidant effects. The purpose of this study was to determine whether ginseng could influence the course of the disease experimental autoimmune encephalomyelitis (EAE), an animal model of MS. C57BL/6J mice were immunized with MOG((35-55)) peptide to induce EAE. After clinical disease appeared, mice received either oral doses of an aqueous extract of ginseng (150 mg/kg body mass), or the vehicle. Clinical symptoms were recorded, and spinal cord tissue samples were analyzed for pathological signs of disease. The aqueous extract of ginseng significantly decreased (i) clinical signs of EAE, (ii) levels of circulating TNF-α, and (iii) central nervous system immunoreactive iNOS and demyelination scores, without a change in other neuropathological measures. This study shows that an aqueous extract of ginseng may be able to attenuate certain signs of EAE, suggesting that it may be a useful adjuvant therapy for MS.