Skin penetration amounts of a highly lipophilic drug, ufenamate, prepared in four oily vehicles, including white petrolatum (WP), liquid paraffin (LP), isopropyl myristate (IPM), and isocetyl stearate (ICS), were compared. Ufenamate was mixed in each vehicle at 5% and applied at a rate of 2 mg/cm2 to intact, stripped, and delipidized Yucatan micropig skin. The amounts of ufenamate and IPM in the stratum corneum (SC), epidermis, and dermis were determined. The skin penetration amounts of ufenamate from liquid oils were significantly higher than those from WP; the amounts of ufenamate were in the order WP<LP≤ICS<IPM, which was the same as that of the vehicle viscosities. The IPM skin penetration amount was approximately 20 times that of ufenamate. The skin penetration amounts of ufenamate from the liquid vehicles decreased after application to delipidized skin and were not significantly different among the four vehicles. The skin penetration amounts of the vehicle oils were significant and might disrupt intercellular lipid structures, especially in the strips 1-6 of the SC. In the deeper SC, there was no effect of the vehicle or skin condition. Thus, ufenamate mixed in liquid vehicles was found to be an effective dosage form.