Background: Experimental autoimmune encephalomyelitis (EAE) serves as an animal model for certain neuroinflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). EAE is accompanied by transient weakness or paralysis of hind limbs. Methods: Dark Agouti (DA) rats were used to investigate the effect of CNS damage in EAE on the skeletal muscles. The course of the disease was followed for 20 days (one relapse) and 30 days (two relapses). After development of maximal clinical signs the animals were treated with olive leaf polyphenols (OLP, 1 g/kg, i.p.) and sacrificed the 20th day from the induction of EAE. TBARS, carbonyl protein levels and glutathione peroxidase (GPX) activity were measured and electrophoretic methods and pathohistological examination of muscle tissue were performed in skeletal muscles gastrocnemius, tibialis anterior and soleus. Results: SDS-PAGE showed differences in muscle protein expression. Western blot analysis determined the expression of the glucose transporter 4 and immunofluorescence microscopy showed the success of GLUT4 translocation. Pathohistological findings of skeletal muscles showed abnormal muscle fibers in EAE, denervation, inflammation and inflammatory infiltrates at the time of the second relapse and regeneration with OLP therapy. Conclusion: Improvement of GLUT4 translocation and incorporation into the cell membrane under the influence of OLP therapy was not observed relative to the control group. However, we propose these bioactive phenolic compounds for therapeutic application in autoimmune and neurodegenerative diseases including MS.