Opportunistic pathogen Pseudomonas aeruginosa is a model microorganism used in explaining cell-to-cell signaling system, named Quorum Sensing (QS). In chronic P. aeruginosa infections, bacteria survive in biofilm and defend themselves against host defense mechanisms by different virulence factors. Three known QS systems, las, rhl and quinolones are basically responsible for the production of virulence factors. Experimental animal models are commonly used in examining in vitro and in vivo behaviors of the bacteria, and explaining interactions between host, bacteria and antibacterials. Among these, chronic pulmonary infection model, applied by administration of agar-impreagnated bacterial suspensions into trachea, is special because it mimicks the biofilm, a virulence factor. Comparative studies conducted particulary with QS wild-type and QS mutant strains, provide important information for understanding the pathogenesis of infection. In this article, the role of P. aeruginosa QS system in the experimental model of chronic lung infection is focused.