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 Introduction: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis distinguished by infiltration of leukocytes into the central nervous system. Changes in composition and levels of unsaturated fatty acids, affect the integrity of blood-brain barrier. In this study, we evaluated the effect of Sesame oil on the leukocyte infiltration into the brain of MOG35-55 induced EAE male C57BL/6 mice. Materials and Methods: In this experimental study, male C57BL/6 mice were placed in two therapeutic groups (n=10 per group) with age and weight-matched as follow: 1.Sesame oil-treated EAE mice received 4ml/kg/day of Sesame oil given i.p. from day -3 until day +19 after disease induction, 2.Non-treated EAE mice (EAE control) received Phosphate buffer alone with same schedule. EAE was induced by immunization of mice with MOG35-55 peptide and complete Freund's adjuvant. Leukocytes infiltration into the brain was investigated 20 days after immunization. Data was analyzed using Mann-Whitney U test. Results: The results show that Sesame oil-treated mice had significantly less clinical score of EAE (2.6±0.4) than non-treated EAE induced mice (4.2±0.6), (p<0.001). Also, there was a significant difference at number of the infiltrating cells in brain between Sesame oiltreated (80±20) and non treated EAE-induced mice (150±30), (p<0.01). Conclusion: These results indicate that Sesame oil reduces infiltration of leukocytes into the brain of EAE mice, therefore lessening the histological changes and clinical signs and thus ameliorating the disease.