Background: The present work was planned with a view to prepare niosomes of an Abacavir sulfate (antiviral drug) and incorporate them into suitable gel base to improve the residance time of the drug in skin layers, while decreasing the systemic absorption of drug.. Hypothesis: The niosomal drug delivery of abacavir sulfate will improve drug permeation. Methods: Film hydration method was used to prepare the niosomes.. 32 Factorial design was used to optimized the niosomal formulation with two independent variables of span 60 and cholesterol amount. The properties like microscopic size, entrapment efficiency, and zeta potential were evaluated for the niosomes. The data was statistical analysed using DOE. The optimized batch of niosomal formulation was incorporated in gel base for topical application. The niosomal gel was tested for controlled drug release from the niosomes.