In this study, a simple and selective gas chromatography-mass spectrometry method was developed and validated for the determination of pogostone in canine plasma. Liquid-liquid extraction was used to separate pogostone from canine plasma, and the mean extraction recovery rates of pogostone and the internal standard (isoalantolactone) were 80.61 and 75.89%, respectively. Plastic centrifuge tubes were inadequate for the plasma sample treatment procedure because of the adsorption effect of pogostone on the inner surface. The chromatographic separation was performed on a capillary column of Agilent HP-5ms, and the spectrometer was operated in an electron-impact ionization with an electron multiplier voltage mode. The standard curve was linear over the concentration range of 1.02-406 ng/mL (r > 0.99). The intra- and interday accuracies for pogostone at four concentrations were 97.77-99.92% and 98.51-100.22%, respectively. The relative standard deviations were <15%. The method was successfully applied to a pharmacokinetic study after the oral administration of pogostone to beagle dogs.