Resveratrol, the main active polyphenol in red wine, has been demonstrated to show benefits against skin disorders. The bioavailability of orally administered resveratrol is insufficient to permit high enough drug concentrations for systemic therapy. In this study, we examined the feasibility of the topical/transdermal delivery of resveratrol. The effects of vehicles on the in vitro permeation and skin deposition from saturated solutions such as aqueous buffers and soybean oil were investigated. The general trend for the delivery from solutions was: pH 6 buffer=pH 8 buffer>10% glycerol formal in pH 6 buffer>pH 9.9 buffer>pH 10.8 buffer>soybean oil. A linear relationship was established between the permeability coefficient (K(p)) and drug accumulation in the skin reservoir. Viable epidermis/dermis served as the predominant barrier for non-ionic resveratrol permeation. On the other hand, both the stratum corneum (SC) and viable skin acted as barriers to anionic resveratrol. Several prototype hydrogel systems were also studied as resveratrol vehicles. The viscosity but not the polarity of the hydrogels controlled resveratrol permeation/deposition. Piceatannol, a derivative of resveratrol with high pharmacological activity, showed 11.6-fold lower skin permeation compared to resveratrol. The safety profiles of resveratrol suggested that the hydrogel caused no SC disruption or skin erythema. It was concluded that delivery via a skin route may be a potent way to achieve the therapeutic effects of resveratrol. This is the first report to establish the permeation profiles for topically applied resveratrol.