Multiple sclerosis is an inflammatory and neurodegenerative disease of the central nervous system in which the immune cells attack the myelin sheath of the nerves, leading to axonal damage, inflammation, immune cell infiltration, and demyelination of the brain and spinal cord. These detrimental changes cause some impairments, such as depression, motor deficit, and cognitive dysfunction, affecting the quality of life in MS patients and their social activities. The present study assessed the impact of 6-week voluntary exercise prior to disease onset on the expression of Nrf-2, IL-10, IL-17, as well as the degree of lymphocyte infiltration in the spinal cord and disease severity in the chronic period of the EAE (30 days post-induction). The results showed that voluntary wheel running stimulated the expression of Nrf-2 and IL-10, while decreased the expression of IL-17, the rate of lymphocyte infiltration, and the severity of EAE at the chronic period of the disease. Thus, alterations in lifestyle, such as regular exercise, may modulate inflammation and disease severity in patients with MS.