AIM The present study was designed to determine whether epimedium flavonoids (EF) had effect on the development of experimental autoimmune encephalomyelitis (EAE) in rats and to elucidate its underlying mechanisms.METHODS EAE was induced by irnmunization of adult female Lewis rats with partially purified myelin basic protein (MBP) prepared from guinea-pig spinal cord homogenate.EF was administrated intragastrically once a day after immunization until day 14 post immunization.Histopathological staining, enzyme-linked immunosorbent assay (ELISA), biochemical methods and western blotting approaches were used to evaluate the disease incidence and severity, neuroinflannnatory and neurotrophie response in the central nervous system.RESULTS Intragastrical administration of EF (20 and 60 mg· kg-1) significantly reduced clinical score of neurological deficit in EAE rats;alleviated demyelination and inflammatory infiltration ; and inhibited astrocytes activation, production of proinflammatory molecules such as interleukin-lβ (IL-13), tumour necrosis factor-α, nitric oxide and nuclear transcription factor in the spinal cord of EAE rats.Treatment with EF also enhanced the expression of 2, 3-cyclic nucleotide 3-phosphohydrolase and nerve growth factor, increased the number of oligodendrocytes and protected the ultrastructure of myelin sheaths and axons in the spinal cord of EAE rats.CONCLUSION Our results showed that EF inhibited the development of partial MBP-induced EAE in rats.This effect involved reducing neuroinflammation and enhancing myelination and neurotrophins and our findings suggest that EF may be useful for the treatment of multiple sclerosis.