In order to get across the intact skin, drug-laden carriers have to pass through narrow, confining pores of 50 nm or less diameter, under the influence of a suitable transdermal gradient. Novel ultradeformable carriers, the elastic liposomes achieve this target via its deforming and self-optimizing property. The main goal of this work was to prepare and characterize, elastic liposomes bearing melatonin, an anti-jet lag agent for its efficient transdermal delivery. Elastic liposomes bearing melatonin were prepared by modified extrusion method and characterized for shape, lamellarity, size distribution, percent drug loading, turbidity profile by Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Mini-column centrifugation and Nephelometric techniques. The effect of different formulation variables like type of surfactant and concentration of surfactant on the deformability of vesicles, turbidity changes, transdermal flux across human cadaver skin, amount of drug deposited into the skin were investigated. Confocal laser scanning (CLS) micrographs revealed that probe (Rhodamine Red) loaded elastic liposomes were able to penetrate much deeper than the probe loaded conventional rigid liposomes. Out of the three surfactants utilized namely, Span 80, Sodium cholate and Sodium dodecylsulphate, formulation bearing Span 80 at an optimum lipid: surfactant ratio of 85:15% w/w proved to be the best in all parameters studied. The optimum skin permeation profile including greater transdermal flux and lower lag time of melatonin from optimized elastic liposomes via human cadaver skin was observed. Our results of the present study demonstrated the feasibility of elastic liposomal system for transdermal delivery of this anti- jet lag agent, which provides better transdermal flux, higher entrapment efficiency, greater skin drug deposition and possesses the ability of a self-penetration enhancer as compared to conventional liposomes.