In this study, we examined the in vitro interaction of Staphylococcusaureus (S.aureus) with culture of peripheral blood monocyte macrophage cells (PBMC) and polymorphnuclear leukocytes (PMNs). Also we studied the possible effects of enrofloxacin against S.aureus inoculation. In the experimental groups, culture supernatants of non-stimulated and Staphylococcal-stimulated PBMC were collected after 1hr, 2hr and overnight incubation to each of the 3 treatments. Measures evaluated for cultured PBMC at each interval were nitric oxide (NO), lysozyme, while cultured PMNs function was assessed after 30min of inocubation by cytochrome-c reduction assay. Moreover, samples of cultured PBMC were also taken for the determination of DNA fragmentation. The study showed that the interaction between S. aureus and cultured monocytes resulted in significant increase of nitric oxide and lysozyme but in stead this effect is declined following enrofloxacin treatment. Fragmentation of DNA of cultured Staphylococcal- stimulated monocytes was quantified colorimetrically by diphenylamine (DPA) assay exhibited significant DNA fragmentation after overnight incubation compared with low fragmented DNA pattern with enrofloxacin treatment. Data concerning the production of superoxide anion within PMNs by cytochrome c reduction assay only appear to induce significant elevation upon treatment with enrofloxacin. The results of the current experiment suggest that enrofloxacin appears to be effective in vitro killing against S.aureus isolate as can be indicated through modulation of bactericidal phagocytic mediator level and activity. The present data may, therefore, raise interesting questions about potential, expected consequences of a prolonged use of fluoroquinolones for therapeutic or prophylactic purposes in induced bacterial infections.