Fourie transform infrared/attenuated total reflection analysis demonstrated that the absorbance intensity of C = O stretching bands, which reflect the amounts of lipids in the stratum corneum, decreased with an increase in the duration of skin treatment with 0.15 M oleic acid/propylene glycol (PG) system, suggesting that the oleic acid/PG system induced the lipid extraction, which was followed by a reorganization of the stratum corneum structures. The spectral peaks which originated from the PG molecule were detected in dermal tissues after 30 min of treatment of the stratum corneum with the same system. This observation suggested that the reorganization of the lipid domains due to the lipid extraction by the oleic acid/PG system helped the PG molecules enter the dermal tissues. It was also suggested that an effective volume within the stratum corneum for solutes and/or solvents which could penetrate through the inter-, and/or intracellular routes could be altered in conjunction with the structural changes of the lipids.