Abstract : Mometasone furoate (Mome) is a topically applied glucocorticoid with very potent anti-inflammatory effect. Although it is a water insoluble drug, systemic absorption might take place if used to large areas causing moderate side effects. The aim of this study is to formulate a nanosuspension based-gel formulas of this drug to reduce the tendency for systemic absorption. These formulas were prepared by solvent-antisolvent precipitation method using probe sonicator instrument and four stabilizers (PVA, PVP, Poloxamer188 and Tween 80). The stabilizer type, drug:stabilizer ratio, addition of co-stabilizer, sonication power and sonication time. The nanosuspensions particle size, polydispersity index and zeta potential were evaluated to select the most stable formulas. Mome optimized formulas were freeze-dried and further characterized using FTIR, DSC, PXRD and SEM. Then they were incorporated in Carbopol 940 gel base to prepare Mome nanosuspension gels (GF1-GF4) at a concentration of 0.1% w/w to be evaluated for pH, viscosity, drug content, in vitro drug release and ex vivo skin permeation test. FTIR revealed the absence of interactions between drug and polymers used. DSC and PXRD demonstrate the reduction of powder crystallinity with some amorphization. Drug release study showed appropriate drug release from the gel base (more than 90% within 3 hrs). Ex vivo permeation study highlighted the ability of nanosuspension based-gel formulation GF2 to increase permeation and localization of mome in comparison with Elica cream (marketed product). This research declares the ability of nanosuspensions to increase localization of (Mome) within skin with minimum systemic absorption.