Herb couple has special clinical significance in reducing the toxicity and increasing the efficacy of drugs. The combination of Radix Angelicae Dahuricae (Baizhi, BZ) and Rhizoma chuanxiong (ChuanXiong, CX) is a traditional herb couple. The combination is better than the CX extract alone in the treatment of migraine for thousands of years, the specific compatibility mechanisms are still unclear. Ligustilide, DL-3-n-butylphthalide and senkyunolide A are the major active ingredients in CX and BZ-CX decoction. However, a comprehensive study of the pharmacokinetics of CX has not been carried out. A gas chromatography-mass spectroscopy (GC-MS) method with high selective, sensitive and accurate was developed. An SH-Rxi-5Sil (30 m × 0.25 mm ID, and 0.25 μm film thickness) column was employed in the GC separation. Selectivity, linearity, precision, accuracy, recovery, matrix effect and stability were used to validate the current GC-MS method. Using the validated method, it is the first time to study on comparative pharmacokinetics of ligustilide, DL-3-n-butylphthalide and senkyunolide A from CX alone and BZ-CX decoction in rat plasma. The pharmacokinetic parameters (C , T , T , AUC , AUC and CLz/F) of all the detected ingredients showed significant differences between the two groups (P < 0.05). The results are helpful for further investigation of the compatibility mechanism of BZ-CX decoction.