Abstract The effects of a number of penetration enhancers such as Azone, N-methylpyrrolidone, propylene glycol and oleic acid on the percutaneous absorption of heparin sodium salt through excised human skin were investigated. Franz-type diffusion cells were used for in vitro permeation experiments. Using skin pre-treated with the penetration enhancers, N-methylpyrrolidone, Azone and propylene glycol promoted heparin flux while oleic acid failed to do so. Studies of aqueous heparin solutions containing such enhancers confirm the enhancement effect of N-methylpyrrolidone and Azone while propylene glycol solutions do not increase heparin flux through the skin. Notwithstanding the high molecular weight of heparin, it does not seem to constitute a limiting factor for the efficiency of N-methylpyrrolidone and Azone.