Liposomes have been frequently used in attempts to enhance percutaneous absorption of several compounds like diclofenac, betahistidine, tetracaine and triancinolone. No detailed explanations are available about the mechanism by which such large entities as liposomes can cross the skin layers more efficiently than smaller molecules. It has been proposed that a follicular pathway contributes to the liposomal delivery of drugs into the deeper skin strata. Liposomes delivery through skin is very dependent on size. Schramlova et al. reported that liposomes up to 600 nm in diameter penetrate through skin rather easily, whereas liposomes with 1,000 nm and more remain interiorized in the stratum corneum. Although the stratum corneum is widely recognized as the main barrier to percutaneous absorption, it is also considered as the main route for penetration. However, recent reports have suggested that, besides the transepidermal route, hair follicles and sebaceous glands may significantly contribute to transdermal delivery.