Five microemulsions were prepared with a mean radius of the internal phase droplets varying from 10 to 70 nm. The microemulsions were evaluated for their ability to deliver a model hydrophilic solute (sucrose) across hairless mouse skin in vitro. Maximum sucrose fluxes, following application of the different microemulsions for 9 h, were similar and were about an order of magnitude greater than that from a 20 mM sucrose aqueous solution. The five (unloaded) formulations and three controls (water, propylene glycol and 5% oleic acid in propylene glycol) were applied for 3 h to the ventral forearm of six volunteers. Transepidermal water loss (TEWL) and relative skin blood flow (SBF) were measured immediately after removing the formulations and repeatedly over a further 3 hour period. SBF increased significantly only after application of the oleic acid/propylene glycol positive control; for all other treatments, SBF remained at the pretreatment value. Immediately after removing all the formulations, TEWL was elevated. However, these values quickly recovered to the pretreatment control except in the case of oleic acid/propylene glycol. Overall, this preliminary study indicates that microemulsion formulations can be used to improve the delivery of hydrophilic solutes while eliciting insignificant effects on human skin in vivo.