Abstract: Sesame oil was evaluated in the treatment of in C57BL/6 mice. It has profound anti-inflammatory activity and been traditionally used to treat inflammatory disorders. EAE was induced by immunization of 6-8 week old mice with MOG35-55 with complete Freunds adjuvant. Therapy with sesame oil was started on day 3 before the immunization. Total Antioxidant Capacity (TAC) was assessed by Ferric Reducing-antioxidant Power (FRAP) method. Nitric Oxide (NO) production was also estimated by Griess reaction. For histological analysis, mice brain was harvested and sections were stained with Hematoxylin-Eosin. After daily intraperitoneal dosage the sesame oil significantly reduced the clinical symptoms in C57BL/6 mice with EAE. Also, treated mice displayed a significantly delayed disease onset compared with control mice. Sesame oil significantly increased TAC, but it’s effect on serum nitrite production was not significant. Typical brain leukocyte infiltration was observed in control mice compared with treated mice. Present results suggest for the first time that sesame oil therapy may be effective in the prevention of symptomatic EAE. This resistance to encephalomyelitis may be associated with inhibition of oxidative stress.