Objective To investigate the neuroprotective effects of artesunate on experimental autoimmuneencephalomyelitis (EAE) and on autophagy in mice. Methods Forty-eight female C57BL/6 mice were randomly dividedinto four groups: control group, model group, and artesunate low- and high-dose groups, with 12 mice in each group. TheEAE model was induced by MOG35-55 peptide. The mice in the low- and high-dose groups were intraperitoneally injectedwith artesunate (10 or 50 mg/ (kg·d)) for 10 consecutive days. The symptoms of the mice in each group were observed.Demyelination lesions in the brain tissues were observed by luxol fast blue (LFB) staining. The expression levels ofautophagy protein markers LC3-I and LC3-II were detected through western blot analysis. Results ①The mice in thecontrol group did not develop neurological symptoms. The mice in the model group and artesunate groups developed tovarying degrees of gait instability, hindlimb weakness, and paralysis. Compared with the model group, the latent period andpeak period were delayed and neurofunctional deficiency scores were decreased in the artesunate groups. The effects in thehigh-dose group were more pronounced than those in the low-dose group ( P < 0. 05). There was no significant difference inpeak period between the low- and high-dose artesunate groups ( P > 0. 05). ② LFB staining showed that the myelin sheathof brain tissue in the model group was loose, disordered, and had low staining intensity, while these findings were improvedin the artesunate groups. ③ Western blot analysis showed that the optical density values of LC3-I, LC3-II, and LC3-II/LC3-I in the model group were higher than those in the control group ( P < 0. 01). These values were lower in the artesunategroups than in the model group ( P < 0. 01), and the findings in the high-dose artesunate group were more pronounced thanthose in the low-dose artesunate group ( P < 0. 05). Conclusions Artesunate has neuroprotective effects on EAE mice andcan reduce demyelination in brain tissue. The mechanism involved may be related to the alleviation of autophagy by downregulation of LC3-I, LC3-II, and LC3-II/ LC3-I expressions.