This study aims to prepare a novel curcumin ethosomes and investigate its properties as a drug delivery system of curcumin. A new modified method combining thin-film hydration and ultrasound was used to prepare ethosomes. Particle size was determined using Mastersizer 3000 laser diffraction analyzer. Average particle size was calculated based on the measurements of five different batches of ethosomes. Free curcumin was isolated by ultracentrifugation to determine the entrapment efficiency. High performance liquid chromatography (HPLC) was performed to determine the concentration of curcumin. The average particle size of curcumin ethosomes decreased with the increase of ethanol concentrations, whereas it increased with the increase of phospholipid concentration. The entrapment efficacy increased with the increase of ethanol and phospholipids concentration. The particle size of the curcumin ethosomes decreased with the increase of ethanol concentration, and increased with the increase of phospholipids contents. The concentration of ethanol and phospholipids showed a positive impact on entrapment efficiency. Finally, curcumin ethosomes showed high entrapment efficiency and good percutaneous permeability. Key words: Ethosomes, curcumin, liposome, high performance liquid chromatography (HPLC).