Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with unknown etiology. Neurotrophins are polypeptides belonging to the neurotrophic factor family. Neurotrophins mediate cell survival and proliferation in the nervous system. In this study, we determined the production of various neurotrophins, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and glial cell-derived neurotrophic factor (GDNF) in Cuprizone model of demyelination. Materials and Methods: In order to induce demyelination, animals were treated by Cuprizone. The mice were divided into three groups. The first group was treated by Cuprizone for 5 weeks. The second group was treated by Cuprizone for 5 weeks and normal diet for 1 week. The third (control) group received normal diet for 6 weeks. After the mice were sacrificed, cerebral corpus callosum was removed and evaluated for expression of neurotrophic factors by real time PCR and histological evaluation. Results: After five weeks, we detected a significant increase of BDNF and GDNF compared to the control group. No changes were observed in CNTF expression. After six weeks, expression of BDNF and GDNF were decreased but they had still higher levels compared to control group. Conclusion: This study suggests that neurotrophins may play a role in pathogenesis of MS.