In the present study, novel ultradeformable liposomes (menthosomes; MTS), deformable liposomes (transfersomes; TFS) and conventional liposomes (CLP) were compared in their potential for transdermal delivery of meloxicam (MX). MTS, TFS and CLP were investigated for size, size distribution, zeta potential, elasticity, entrapment efficiency and stability. In vitro skin permeation using hairless mice skin was evaluated. Vesicular morphology was observed under freeze-fractured transmission electron microscopy (FF-TEM). Intrinsic thermal properties were performed using differential scanning calorimetry (DSC) and X-ray diffraction. The skin permeation mechanism was characterized using confocal laser scanning microscopy (CLSM). The results indicated that the difference in physicochemical characteristics of MTS, TFS and CLP affected the skin permeability. MTS and TFS showed higher flux of MX than CLP. CLSM image showed deformable vesicles mechanism for delivery of MX across the hairless mice skin. Our study suggested that ultradeformable and deformable liposomes (MTS and TFS) had a potential to use as transdermal drug delivery carriers for MX.Key words menthosome; transfersome; liposome; skin permeation; meloxicam; menthol Meloxicam (MX), a cyclooxygenase-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID), is used to treat rheumatoid arthritis, osteoarthritis and other joint diseases. The injectable and oral administrations of NSAID drugs are not appropriate for needle-phobia and peptic ulcer patients. Moreover, the major limitation of MX is its low aqueous solubility (0.012 mg/mL in water and 0.086×10 −2 mg/mL in 0.1 M HCl) 1) with log P 1.91 and 0.07 at pH 5.0 and 7.4, respectively. MX delays its absorption from gastrointestinal tract (GI) and its prolonged use is associated with the incidence of GI side effects (bellyache, indigestion, ulceration and bleeding).2) If MX could be delivered without incidence of these limitations, MX administration would become safer and more acceptable. MX is suitable for development as a transdermal delivery candidate.Transdermal drug delivery or skin delivery has become a global priority because the conventional drug administration is associated with numerous limitations. Liposomes are one of potential strategies that utilize for skin delivery of hydrophilic drugs, 3) lipophilic drugs, 4) protein 5) and macromolecule.6) Although last decades, some design of conventional liposomes are of little or no value as carriers for transdermal drug delivery, but rather remain confined to the upper layer of the stratum corneum. However, recent approaches in vesicular modulating drug delivery through skin have resulted in many designs of novel vesicular carriers e.g., deformable liposomes (transfersomes), 7) niosomes, 8) ethosomes, 9) invasomes, 10) flexosomes 11) and menthosomes. 12) Transfersomes are the first generation of elastic vesicles introduced by Cevc and Blune 7) and consist mainly of phospholipids and an edge activator or a single-chain surfactant which having a high radius of curv...