TCM has some advantages over western medicine in delaying the progress of MS/EAE due to its characteristics of multiple targets, overall regulation and less toxic side effects. Qi deficiency and Blood stasis syndrome is one of typical phenomenon in MS/EAE. AST-IV can significantly relieve clinical symptoms of EAE by supplementing qi and promoting blood flow. To investigate the efficacy and mechanism of AST-IV in the treatment of EAE. Female C57BL/6 mice were induced to establish EAE model by myelin oligodendrocyte glycoprotein peptides (MOG35–55), which were randomly divided into EAE group, high-dose and low-dose AST-IV group. After 3 days of modeling, the mice were injected with drug till day 28. High-dose and low-dose AST-IV group were intraperitoneally injected with AST-IV 30 mg/kg/day and 15 mg/kg/day respectively. The injection of PBS was set up as control in a similar manner. High-dose and low-dose AST-IV could significantly reduce the average highest clinical score and alleviate the clinical symptoms of EAE. AST-IV inhibited the inflammatory cells in spinal cord. Flow cytometry analysis showed that AST-IV significantly increased the proportion of CD4+ CD25+ and CD4+ TGF-β+, decrease the proportion of CD4+IL17+, inhibiting the expression of TLR4, Myd88 and NF-kappa B/p65 in spinal cord. AST-IV is effective on EAE by regulating the inflammatory pathway and maintains the balance between Th17 cells and Treg cells. (NNSF of China 81473577, Collaborative Innovation Center Project of Astragalus Resource Industrialization and Industrial Internationalization-hqxtcxzx2016-020. Ma and Xiao are corresponding authors).