Ethosomes are amphiphilic novel lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Mefenamic acid is anthranilic acid derivative agent and belongs to Biopharmaceutical classification system class II drugs that show poor water solubility as well as poor lipophilic character. Oral use of Mefenamic acid contraindicated resulting from sever side effect, thus topical administration is recommended. The present research work Ethosomal vesicles were successfully developed through hot method under stirring and sonicated and evaluated DSC thermograms, Particle size distribution, Vesicles shape, In-vitro Permeation study and Stability study. The present study demonstrates that the ethosome vesicle found to be Particle size distribution was found good. Stability study was found 97.85%, 98.69% and 98.43% as respectively. In vitro drug release 94.509%, 95.957% and 88.068% respectively as per formulation (MET1, MET2, and MET3). The entrapment of drug in vesicles found to be 57.98%, 67.26% and 33.19 % respectively, solubility and availability of drug at the site.