Propofol (PF), a highly lipophilic anesthetic, has several desirable properties, such as the rapid onset and cessation of its effects upon intravenous infusion. In this study, the transdermal absorption of PF was investigated with the aim of the development of an alternative route of administration. PF solutions containing isopropyl myristate (IPM), ethanol or propylene glycol (PG) at various concentrations were prepared and applied to the abdominal skin of rats. Petrolatum and fatty alcohol propylene glycol (FAPG) ointments containing PF were also prepared and applied to the dorsal skin. Eyelid opening was measured and the ratio of the measured value to the initial value was calculated to evaluate the level of the pharmacological effect of the preparation. The PG solution containing 80% PF achieved higher plasma PF concentrations than the 100% PF solution. The PF-FAPG ointment produced a higher plasma PF concentration than the PF-petrolatum ointment. Furthermore, a drowsy state was confirmed after transdermal administration of 42% PF-FAPG ointment. These results indicate that the combination of PF and PG was appropriate for the transdermal absorption of PF, and PF was absorbed through the rat skin to an extent sufficient to cause a continuous sedative effect.