Abstract: AimTo test the enhancing activity and the mechanism of oleyl pyroglutamate used as transdermal enhancer. MethodsThe penetration-enhancing effects of oleyl pyroglutamate, oleyl alcohol and oleic acid on the three drugs (caffeine, tinidazole and cortisone) were observed; the transdermal enhancing mechanism of oleyl pyroglutamate was studied with the attenuated total reflectance Fourier-transfer infrared spectroscopy(ATR-FTIR) of the human stratum corneum in vivo. ResultsThe penetration-enhancing ratio of the three drugs was 7.9 fold, 41.8 fold and 2.8 fold, respectively. The absorptions at 2 800-2 950 cm^-1 and 1 642-1 646 cm^-1 (amide-I) in the ATR-FTIR spectrum of the stratum were found to be shifted differently following removal of the stratum corneum which was treated with oleyl pyroglutamate. ConclusionOleyl pyroglutamate showed better penetration-enhancing effect on the penetration of drugs. Its transdermal enhancing mechanism may be that oleyl pyroglutamate induced not only disordering of the stratum corneum lipid, but also change of the secondary structure of keratin.