The present study was designed to evaluate skin permeation enhancement effect of essential oils from Ligusticum chuanxiong HORT (chuanxiong oil) in rabbits and to compare the in vivo absorption and in vitro permeation using flurbiprofen as a model drug. In vivo results demonstrated that chuanxiong oil showed a rapid and marked permeation enhancement effect. The group with 10% oil exhibited the highest value of area under the curve (AUC) of 418±124 μg/ml·h, which was 2.43 times the high of control. The AUC value of 3% oil group (245±81.6 μg/ml·h) was similar to that of 5% oleic acid group (235±74.5 μg/ml·h). Whereas in vitro results indicated the enhancement of chuanxiong oil was relatively weak. The group with 3% oil appeared to the highest flurbiprofen flux (84.9±19.3 μg/cm²/h), to some extent lower than 5% oleic acid group (107±5.85 μg/cm²/h). At 10% and 15% concentrations, chuanxiong oil even decreased the flux of flurbiprofen compared with the control. Both in vitro results with pretreated skin and flurbiprofen content accumulated in skin indicated the potential mechanism for the in vitro enhancement of chuanxiong oil was the weakened barrier function by improving in the partitioning of flurbiprofen to the stratum corneum. The discrepancy was noted between the in vivo and in vitro results, indicating only about the weakened barrier function was not enough to explain the sharply increment of in vivo absorption of flurbiprofen by chuanxiong oil. The GS-MS results indicated phthalides identified from chuanxiong oil might mainly contribute to enhance in vivo absorption of flurbiprofen because of its large quantities (91.15%).