The present study describes the production and characterization of phosphatidylcholine based ethosomes and organogels, as percutaneous delivery systems for crocin. Crocin presence did not influence ethosome morphology, while the drug slightly increased ethosome mean diameter. Importantly, the poor chemical stability of crocin has been found to be long controlled by organogel. To investigate the performance of phosphatidylcholine lipid formulations as crocin delivery system, in vivo studies, based on tape stripping and skin reflectance spectrophotometry, were performed. Tape stripping results suggested a rapid initial penetration of crocin exerted by the organogel, probably due to a strong interaction between the peculiar supramolecular aggregation structure of phospholipids in the vehicle and the lipids present in the stratum corneum and a higher maintenance of crocin concentration in the case of ethosomes, possibly because of the formation of a crocin depot in the stratum corneum. Skin reflectance spectrophotometry data indicated that both vehicles promoted the penetration of crocin through the skin, with a more rapid anti-inflammatory effect exploited by ethosomes, attributed to an ethanol pronounced penetration enhancer effect and to the carrier system as a whole.