Objective To explore the effect of vasoactive intestinal peptide (VIP) on the content of IL-17A in the brain tissue of rat models of experimental autoimmune encephalomyelitis (EAE). Methods Sixty healthy female Wistar rats were randomly divided into normal control group, EAE control group, low-dose VIP group and high-dose VIP group. Ten healthy guinea pigs were used to prepare anti- IL-17A antibody. Myelin basic protein (MBP)+complete adjuvant (CFA) were used to establish the EAE model. Since the first day of modelling, the low-dose and high-dose VIP groups received intraperitoneal injection of VIP 4 nmol/kg (0.2 mL) and 16 nmol/kg (0.8 mL), respectively, every other day for 10 consecutive days. The normal control group and EAE group were injected with 0.8 mL saline instead of VIP. The incubation period, progression and the peak of neurological dysfunction scores (NDS) of the rats were recorded. The levels of IL-17A in the brain tissue was determined by ELISA assay, and the GFAP⁺astrocyte activation in brain at morbidity peak in the rats was examined using anti-GFAP (glial fibrillary acidic protein) antibodies. Results The incubation period were extended, the progression period was shortened and the peak neuological dysfunction score (NDS) was decreased in the VIP-treated groups, in a dose-response relationship. The cytokine levels of IL-17A and the astrocyte activation degree in brain tissue were reduced in each VIP dose group, in a dose-response relationship. Conclusions VIP exerts therapeutic effect on experimental autoimmune encephalomyelitis through lowering the IL-17A content and inhibition of astrocyte activation in the brain tissue.