The in vitro and in vivo effect of pretreatment by cardamom oil, a crude drug extract, in ethanol/water vehicles on the transdermal delivery of indomethacin was investigated. The cyclic monoterpene components in cardamom oil were also determined and quantified in this study. The permeation of indomethacin was significantly enhanced after pretreatment of cardamom oil both in the in vitro and in vivo studies. The result of various pre-treatment periods showed that the indomethacin flux decreased as the length of the pretreatment increased. Both natural cardamom oil and a cyclic monoterpene mixture composed of the components of the oil showed similar enhancement on indomethacin permeation, indicating cyclic monoterpenes are the predominant components altering the barrier property of stratum corneum. The results also showed that three minor components in cardamom oil (alpha-pinene, 6.5%; beta-pinene, 4.8%; alpha-terpineol, 0.4%) had a synergistic effect with 1,8-cineole (59.3%) and d-limonene (29.0%) to enhance the permeation of indomethacin.