〔Abstract〕 Objective To explore the effect of perampanel regulation of mitogen actived protein kinase(MAPK) signaling pathway after injection of nitroglycerin(NTG) induced migraine rats. Methods Thirty-two male SD rats were randomly divided into four groups with eight in each group: normal saline, NTG group, perampanel 50 μg/kg+NTG group, perampanel 100 μg/kg+NTG group. The time of scratching the head and the number of climbing the cage were observed, the periorbital pain threshold of the rat was measured by the fiber filament, and the photophobia of the rat was observed in the light and dark box experiment. Immunofluorescence was used to detect the rat TGs PACAP expression level; RT-qPCR was used to determine the expression level of PACAP mRNA and ELISA was used to detect the concentration of PACAP in rat blood. Meanwhile, Western blot was used to detect p-p38 MAPK,p-JNK,p-ERK protein expression level in rats TG. Results Compared with the control group, the periorbital withdrawal threshold decreased, the cage climbing behaviors and facial grooming behaviors increased, and the time spent in the light compartment in the light-aversive behaviors decreased in the NTG group, the expression levels of PACAP mRNA and protein increased(P<0.05). While, the perampanel 50 μg/kg+NTG group and the perampanel 100 μg/kg+NTG group increased the periorbital withdrawal threshold, reduced the cage climbing behaviors and facial grooming behaviors, increased the time spent in the light compartment and decreased the expressions of PACAP mRNA and protein in comparison with the NTG group(P<0.05). Compared with the control group, the expression levels of p-p38 MAPK, p-ERK and p-JNK in NTG group increased(P<0.05); compared with the NTG group, the expression levels of p-p38 MAPK, p-ERK and p-JNK decreased in perampanel 50 μg/kg+NTG group and the perampanel 100 μg/kg+NTG group(P<0.05). Conclusion Perampanel may relieve migraine symptoms by inhibiting MAPK signaling pathway.