The chronic inflammatory conditions like psoriasis has an increased prevalence and is linked with various associated life threatening disease conditions. The main objective of this project was to developed a methotrexate-olive loaded nano emulsion. The formulation was assessed for various parameters including Thermodynamic Stability, physico-chemically characterization, drug release kinetics and entrapment efficiency and in vitro/ in vivo skin permeation analysis. Final optimized formulation had a particle size 18.27±5.78 nm with a PDI of 0.25±0.01, whereas the average entrapment efficiency of formulation was 74.68±2.1%. The release kinetics suggested 97.72% drug release at pH 5 after 20 hrs. The FTIR data confirmed that the chemical structure of drug is retained with efficient loading into the formulation. Permeation data showed that an average of 79.23±3.6μg/cm2 of methotrexate was permeated from the nano emulsion with an average flux of 2.326±0.45μg/cm2/h after 24 hrs. Finally in vivo studies on rabbit skin confirmed that the structural changes of intercellular lipid layers in the stratum corneum are not responsible for enhanced skin permeation of methotrexate loaded nano emulsion. It was concluded that olive oil based MTX-NE is suitable for topical application and can be used for management of psoriasis.