Staphyloccocus aureus causes wide range of infections from being mild to crucial problems. Azithromycin macrolide have been in use for many years solving the severity of these infections. But, aqueous insolubility and resistance developed is the question of focus. Considering the need for improvement of the drug properties, we used conventional clove oil based microemulsion drug delivery system for its effective antimicrobial activity and stability of the formulation. This optimized system is prepared using clove oil, tween 20 and water (5:30:65 v/v) by gentle mixing at laboratory environment. The dynamic light scattering technique reports the droplet size range in the nanometer scale with low polydispersity index value. The better quality antibacterial action was further quantified by the liberation of UV absorbing substances at 260 nm confirming structural damage of the treated pathogen. Copyright © 2014 American Scientific Publishers