Objective To observe the effects of different concentrations of baicalin on the mouse model of experimental autoimmune encephalomyelitis (EAE) and to explore its mechanisms. Methods A mouse model of EAE was established with MOG33-55 peptide and bacillus Calmette-Guerin (BGG) vaccine with complete Freund adjuvant (CFA). At the third day after immunization, high and low doses of baicalin were administered to the mice intragastrically once a day for 20 days. The neurological function of mice was evaluated. TUNEL staining was used to detect apoptosis in the spinal cord tissue. The level of ATP in spinal cord tissue was detected by an ATP determination kit. Furthermore, the protein expressions of Bax, Bcl-2, cleaved cas-3 and cleaved cas-9 were detected by western blot, respectively. Results Baicalin improved the neurological function and delayed the onset time in EAE mice.After the treatment with baicalin, the TUNEL staining showed that the number of apoptotic cells in spinal cord was decreased, and the ATP level decreased. Western blot revealed that the protein expression of Bcl-2 was significantly increased, while the protein expression of Bax, cleaved cas-3 and cleaved cas-9 were significantly decreased. Conclusions Baicalin can reduce apoptosis by inhibiting mitochondrial endogenous apoptosis pathway, protect the function of mitochondria and improve the neurological function inEAE mice, therefore, provide experimental evidence for the disease prevention.