Purpose <p>The present study investigated the synergistic effects of aerobic training (AT) and royal jelly (RJ) consumption&#xa0;on oxidant-antioxidant markers in brain tissue of an experimental autoimmune encephalomyelitis (EAE) model.</p> Methods <p>Forty-nine female Sprague–Dawley rats with EAE were divided into seven groups (n = 7 in each group) including EAE, Sham (Sh), 50mg/kg RJ (RJ50), RJ100, AT, AT + RJ50, and AT + RJ100. To investigate the effect of EAE on the variables, 7 healthy rats were selected as healthy control (HC) group. AT was performed for five weeks, four sessions per week at a speed of 11 m/min for 25–35&#xa0;min, and RJ was injected intra-peritoneally at doses of 50 and 100mg/kg/day. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in brain tissue were measured, and the results were statistically analyzed using one-way ANOVA test.</p> Results <p>In the AT group, MDA levels were significantly lower than EAE group (P ≤ 0.05). Also, in the RJ100 group, SOD and GPx levels were significantly higher and MDA levels were significantly lower than EAE group (P ≤ 0.05). In the RJ50 group, MDA levels were significantly lower than EAE group (P = 0.001). In addition, MDA levels in the RJ100 group were lower than RJ50 group (P = 0.011). Also, in the AT + RJ50 and AT + RJ100 groups, SOD and GPx levels were significantly higher and MDA levels were significantly lower than EAE group (P ≤ 0.05).</p> Conclusion <p>It seems that AT and RJ can lead to the strengthening of each other’s effects on increasing antioxidants and reducing oxidative stress. Nevertheless, RJ with a higher dose has much more favorable effects on this pathway.</p>