Abstract: Several technological advances have been made in the recent years to overcome skin barrier properties and to enhance drug penetration. In this regard, transdermal drug delivery system provides a suitable solution of the problems associated with conventional routes of drug administration. In the present study, Withania somnifera leaf extract loaded proniosomal gel was prepared and evaluated for better delivery and improved anti-inflammatory property. The formulated gel was characterized for vesicle physical analysis, entrapment efficiency and in vitro release study. The method used for preparation of proniosomal gel resulted in higher drug entrapment value of 87.2%. Scanning electron microscopy analysis showed that the surface of the particles was smooth. The formulations showed prolonged in vitro drug release of 60.8% over a period of 24 h and significant anti-inflammatory response. From this study, it is concluded that proniosomes are very stable and promising delivery system for Withania somnifera leaf extract.