To explore the application of substance P (SP) in rats mesencephalon to explain the mechanism of acupuncture for migraine.Methods： According to the present studies on change of SP and receptors during the pain and the dominant position of acupuncture for brain diseases， the study prospects and application process based on the change of SP and receptors were introduced. Results： The change of SP and receptors could explain the mechanism of acupuncture for migraine. Conclusion： The application of SP and receptors are supposed to be available ways to explain the mechanism of acupuncture for migraine， which can provide a theory base to clinical research.