The number of products based on new drug delivery systems has considerably increased in the past few years, and this growth is projected to carry on in the future. These biopharmaceuticals present challenges to drug delivery scientists because of their different nature and difficulty in delivery through conventional routes. Therefore, further research will focus on the delivery of these complex molecules through different routes, including nasal, pulmonary, vaginal, rectal, etc. The intend of the study was to formulate and evaluate ethosomes of Sesbania grandiflora leaves which may transport the drug to the targeted site more efficiently than marketed gel preparation and also overcome the problems related to oral administration of a drug. Transdermal drug delivery is a technique that can be exploited to overcome the variables, which could affect the oral absorption of drugs such as pH, food intake, and gastrointestinal motility. As compared to the liposome or hydro-alcoholic solution ethosomal systems were much more capable of delivering a fluorescent probe to the skin in terms of quantity and depth. The formulations were prepared with ethanol, lecithin, propylene glycol, and glycerol and were evaluated. The lecithin (phospholipids) used as a vesicles forming component, polyglycol, and ethanol used as a skin penetration enhancer.