Phospholipids or liposomes are recognized to have skin permeation enhancing ability, although their mechanisms are still controversial. The aim of this study was to establish a method of increasing the skin permeation of active ingredients, using phosphatidylcholine as a permeation enhancer. Caffeine was used as a model active ingredient and in vitro skin penetration experiments were performed using Franz-type diffusion cells to determine the amount of absorbed caffeine. Lipid vesicles were prepared by the microfluidization process. The encapsulation efficiency of caffeine was found to be very low due to the instability of the liposome structure and the water solubility of caffeine. However, the amount of absorbed caffeine was nearly independent of the encapsulation efficiency and the vesicle size, but increased with the increase of phosphatidylcholine concentration. These results indicated that phosphatidylcholine could act as a penetration enhancer, irrespective of its presence in vesicular form or solubilized form.