Objective:To explore the effect of the human mesenchymal stem cells(hMSCs) transplantation on treating experimental autoimmune encephalomyelitis(EAE) rats and the status of transplanted hMSCs in the brain tissue of EAE rats. Methods:hMSCs were isolated from human adult bone marrow. EAE rat models were made, and the human mesenchymal stem cells were transplanted into the rat tail vein 10,15 and 21 days after immunization. The neurological signs were undertaken in all the groups every day after immunization. Rats were sacrificed at different time. The differentiation and migration of the human mesenchymal stem cells in vivo,and the number and status of the demyelinated foci were checked by electronic microscope and immunohistology. Results:Rats that received transplantation had a significant improvement compared with the control group in the observation of electronic microscope. Twenty days later, rats that received transplantation 10 and 15 days after immunization had a significant improvement of clinical outcome compared with the control group(P < 0.05). The number of demyelinated foci decreased significantly(P < 0.05). The human mesenchymal stem cells were induced to differentiate into astrocytes, oligodendrocytes and neurons in vivo. Immunohistological result confirmed that the transplanted stem cells migrated to the demyelinated foci. Conclusion:The human mesenchymal stem cells differentiated into three main types of neural cells by the influcence of the EAE microenvironment signals.Human mesenchymal stem cells transplantation could effectively improve the neurologic function of rats, and decrease demyelinated foci number.