Glucagon-like peptide-1 receptor (GLP-1R) has been indicated to involve in chronic pain, however, the mechanism by which GLP-1R alleviates the central sensitization of chronic migraine (CM) remains unclear. Treatment with GLP-1R agonist liraglutide attenuated trigeminal allodynia and suppressed the protein levels of CM-associated molecules in the trigeminal nucleus caudalis (TNC). Further analysis showed that injection of liraglutide stimulated the release of IL-10 in the TNC. Treatment with IL-10 also alleviated pain hyperalgesia. Our findings illustrated that liraglutide might alleviate the central sensitization of CM by stimulating the release of IL-10, which reveals a novel mechanism of CM.