Objective To investigate the protective effect of RRx-001 on experimental autoimmune neuritis （EAN） and related mechanism.Methods Lewis rats were immunized with a synthetic P2_53-78 peptide mixed with complete Freund’s adjuvant to establish a model of EAN， and RRx-001 was administered by intraperitoneal injection. The rats were divided into control group， model group， and experimental group. Body weight and clinical score were determined to assess disease progression； transmission electron microscopy was used to observe the demyelination of sciatic nerve； blood fluorescein isothiocyanate （FITC）-dextran level was measured to assess intestinal barrier permeability； the levels of nitric oxide （NO）， glutathione （GSH）， and superoxide dismutase （SOD） in the intestinal tract were measured to assess the level of oxidative stress； ELISA kits were used to measure the expression levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α）； flow cytometry was used to analyze CD3⁺ T cells， CD3⁺CD4⁺ T cells， CD3⁺CD8⁺ T cells， CD4⁺CD44H⁺ T cells， CD4⁺CD62L⁺ T cells， and CD11b⁺F4/80⁺ macrophages.Results Compared with the model group， RRx-001 reduced the weight loss and clinical score of EAN rats （P<0.05）， alleviated sciatic nerve demyelination， and improved intestinal permeability by increasing the activity of SOD， reducing the expression levels of IL-1β and TNF-α， and alleviating intestinal damage （P<0.001）； it also reduced the percentages of CD4⁺ T/CD8⁺ T lymphocytes and CD11b⁺F4/80⁺ macrophages and increased the percentage of CD3⁺ T lymphocytes （P<0.05）.Conclusions RRx-001 can improve the clinical symptoms of EAN rats and exert a protective effect on EAN rats possibly by regulating the activation of immune cells and inhibiting the release of inflammatory factors. ［Journal of International Neurology and Neurosurgery, 2023, 50(6): 1-6］