A simple and sensitive HPLC-UV method was developed to determine ligustilide in rat brain samples after nasal administration. The lower limit of quantification (LLOQ) was 245 ng/ml for ligustilide. The calibration curve was linear over a concentration range of 245-4900 ng/ml. Brain samples were obtained at regular time intervals after nasal administration of ligustilide (45 mg/kg). Ligustilide could be detected in rat brain only after 5 min of nasal administration; which showed that ligustilide may have a rapid onset of action. This result illustrates that intranasal administration of ligustilide may act as a promising alternative to conventional routes of administration.