BACKGROUND:: Superoxide dismutase (SOD) and catalase are anti-oxidant enzymes potentially used by the bacteria to neutralize macrophage microbicidal molecules such as hydrogen peroxide (H2O2). OBJECTIVE:: To investigate contribution of bacterial anti-oxidant enzymes in intracellular survival of Staphylococcus aureus (S. aureus) within macrophages. MATERIALS:: Murine peritoneal macrophages and S. aureus (CMC-524, ICH-629 and ICH-757). TREATMENT:: 10 colony forming units (CFU) of the 90 minutes (min) intracellularly viable S. aureus were administered (i.v.) per mouse through 0.1 ml saline. METHODS:: Anti-oxidant enzyme assay, phagocytic activity, H2O2 release, Zymography for catalase, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were estimated. One-way Model I ANOVA and one tail Studentʼs t-test were performed. RESULTS:: Survival of S. aureus was least after 90 min of reincubation within macrophages. Maximum amount of bacterial anti-oxidant enzymes were released after 90 min of re-incubation. H2O2 released after 90 min of re-incubation with S. aureus was maximum. Higher activity of catalase and SOD by S. aureus occurred in response to the gradual production of H2O2. Serum IL-6 and TNF-α was also elevated 1h post infection. CONCLUSIONS:: Bacterial catalase and SOD combat reactive oxygen species enabling S. aureus to persist within macrophages, inducing local inflammation, causing greater induction of serum TNF-α and IL-6.