Ethosomes are non-invasive delivery vehicles for medications that allow them to penetrate deep into the epidermal layers and/or the systemic circulation. Betamethasone valerate is steroid ester which is used to help relieve redness, itching, swelling or other discomfort caused by skin conditions. It is a BCS class II drug (low solubility and high permeability). The objective was to prepare Betamethasone valerate ethosomes and then load them into the gel. The optimized ethosomes formulation was selected to be incorporated in the gel system based on the good stability results and the optimized in-vitro study. In the present work, the ethosomes were prepared by utilizing soya lecithin, ethanol and other useful materials. Ethosomal formulations were prepared by using the cold method. The ethanolic vesicular system composed of phospholipids (15% to 55% w/v), ethanol (20% to 40% v/v), propylene glycol, drug and distilled water. This study reported on the use of a Box–Behnken design in the optimization of ethosomes dispersion mean diameter for the encapsulation of ethosomes. Out of fifteen batches, batch F9 is the optimized batch. The gel was prepared by the use of carbopol 934, triethanolamine and glycerol. Methyl and propyl paraben were used as preservatives. The average particle size of optimized batch is 124.2 nm, PDI is 0.280 and zeta potential is -17.0 mV. The pH of the gel is 5.6 ± 0.03. The in-vitro permeation study is 88.92±0.054% in pH 7.4 Phosphate buffer. The viscosity of the gel is 4980 ± 0.45 cP and the spreadability is 37.88/4 ± 0.05. The gel formulations will be stored at 40˚C and 75% relative humidity for 90 days. Prolonged releases will achieved when they will formulated as topical gels on maintaining the ethosomal structure.