Methotrexate was formulated in nanoemulsion based system with the aim of improving its permeation via skin. double nanoemulsion (w/o/w) was prepared employing phase inversion temperature method. preformulation studies were preformed to evaluate drug-excipient compatibility. solubility of drug in oils and surfactants was determined to identify nanoemulsion components. surfactants were screened for their ability to emulsify selected oily phases. nanoemulsion composed of drug, labrofac, and labrosol enhanced permeability of methotrexate loaded reverse micelle. the nanoemulsion exhibited mean globule size <100 nm, with polydispersity indices below 0.1. diffusion study of the novel nanoemulsions was carried out using franz diffusion cell, in phosphate buffer ph 7.4 showed satisfying skin permeation. at room temperature, they exhibited good physicochemical stability