The two herbs Ligusticum chuanxiong (LC) Hort. (Umbelliferae) and Gastrodia elata (GE) Blume (Orchi-daceae), are widely used in the clinic for the treatment of migraine. This article aims to understand the effects of LC and GE on blood-brain barrier (BBB) permeability in migraine rats. Serotonin, excitatory amino acids (EAAs) and matrix metalloproteinase-9 (MMP-9) were determined at different sampling times to assess BBB disruption during a migraine attack. BBB permeability was examined by fluorescence imaging and Evans blue dye (EBD) extravasation. The results showed that the expression of serotonin in migraine rat brain was enhanced from 30min to 120 min and glutamate (Glu) was suppressed from 30min to 60min in LC-GE group compared with the model group (p< 0.05 or 0.01), while the MMP-9 levels in migraine rat blood was increased at 30min as well as decreased at 120min in LC-GE group compared with the model group (p< 0.05 or 0.01). EBD levels in rat brain were significantly lower at 30∼60 min and 120∼150 min in LC-GE group than that of the model group (p<0.05 or 0.01). Our findings demonstrated that LC and GE might decrease BBB permeability and maintain its integrity through regulating serotonin, EAAs and MMP-9 in migraine rats.