Experimental autoimmune encephalomyelitis (EAE) is characterized by appearance of anti-myelin autoantibodies in the blood and with the increased expression of MHC (major histocompatibility complex) class I and II antigens in the brain tissue. Although there is an evidence of possible linkage between influenza vaccination and development of autoimmune processes, the precise mechanisms of action of this vaccine on EAE-induction is still unclear. In this study, effects of influenza vaccine on clinical sign, antimyelin antibody titer in the blood by ELISA test and expression of MHC class I and II molecules immunohistochemistry were examined in the brain of C57BL mice with EAE. EAE was induced by MOG 35-55 protein in 16 of 32 mice. Influenza split vaccine was administered to eight MOG-induced EAE mice and to eight previously nontreated mice. A significant increase of anti-influenza antibody was detected in vaccinated mice compared to nontreated mice. Also, significant increase of antimyelin antibodies was detected in mice with EAE compared to vaccinated group without EAE and control group, respectively. In EAE-influenza vaccinated mice, a mild but not significant increase of antimyelin antibodies was detected, compared to EAE mice. High expression of MHC-II and mild expression of MHC-I were detected in the brain of mice with EAE. No expressions were detected in vaccinated and normal intact brains. Similar staining was found between EAE-vaccinated and EAE group in both MHC-I and MHC-II expression. The results obtained show that influenza vaccine has no significant influence on EAE induction and severity of autoimmune processes.