Development of curcumin loaded transethosome (TE) based formulation, with statistical optimization tool to enhance and effective dissolved/bioavailable concentration of curcumin for psoriasis treatment, was envisaged in this research work. Curcumin loaded TEs were prepared by “cold method. Critical process parameters were assessed viz concentration of lipid, surfactant & ethanol; temperature and stirring. The TE formulation was planned for statistical optimization by using half fraction design with 2 blocks. The output selected were vesicle size & deformability, zeta potential, entrapment efficiency. The in vitro release profile and in vivo antipsoratic activity were performed by Franz diffusion cell and Imiquimod induced model of psoriasis in animal, respectively. Response surface and corresponding equations revealed that vesicle size the impact temperature (D) square of C (i.e. Ethanol Conc.), D and E (i.e. Stirring rate) were significant (p<0.05). Whereas, zeta potential was associated with A (phosphatidyl choline conc.), B (sodium cholate conc.), C, AD, BE, A² as significant model terms. The TE formulation was characterized with transmission electron microscope, Infrared spectroscopy. In vitro curcumin release study suggested TE-curcumin 84.21 ± 1.83 % release which was more than 2 foldw.r.t. curcumin. In vivo and biochemical studies outcomes were in accordance with enhanced release results and expressed significant higher effectiveness of TE-curcumin in comparison to same concentration curcumin. TECurcumin produced combined prolongs the drug contact time and releases the drug in a controlled manner, which results in improved bioavailability to the effective level for psoriasis indication.