Multiple sclerosis (MS) is a demyelinating disease affecting 2.5 million young people worldwide because of its immune-mediated pathological mechanisms. Recent studies have shown that stem cell transplantation is a new potential therapy for MS. There has been renewed interest in cell therapy to improve quality of life for MS patients. In this study, the experimental autoimmune encephalomyelitis (EAE) model, which is the most commonly model to mimic MS, was successfully established in cynomolgus monkeys. To evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (UCMSCs) on MS, we intravenously transplanted UCMSCs into cynomolgus monkeys with EAE. Our results showed that UCMSC transplantation significantly ameliorated the clinical symptoms of MS. Magnetic resonance imaging and clinical signs indicated that demyelination was obviously decreased after UCMSCs therapy. Moreover, the present study showed that the mechanisms, involved in the effects of UCMSCs on MS, included their immunomodulatory functions to regulate cytokine secretion and affect functional differentiation of the T cell lineage.