Background and Aim:Pasteurella multocida B:2 is the causative agent of hemorrhagic septicemia (HS) in buffalo and cattle. Buffaloes are known to be more susceptible to HS than cattle, but the reason for this remains unknown. This study aimed to compare the in vitro efficiency with which buffalo and cattle macrophages can kill P. multocida B:2.Materials and Methods:Monocyte-derived macrophages of buffalo and cattle were used in this study. They were exposed to 1×106 colony-forming unit/mL of live P. multocida B:2 before the cells were harvested at 0, 30, 60, and 120 min post-exposure and viewed under a fluorescence microscope to count viable and non-viable macrophages and the macrophages with phagocytosing P. multocida B:2 cells. The phagocytosis, intracellular bacterial killing, and macrophage death rates were calculated and compared between the two species and sampling points.Results:In general, the rates of phagocytosis, intracellular killing, and macrophage death increased with time of exposure for both animal species. No significant (p>0.05) differences were noted between the phagocytosis rates by the macrophages of buffalo and cattle throughout the experiment. However, the rates of intracellular killing were significantly (p<0.05) higher in cattle macrophages at 30 min and 120 min post-exposure than those of buffalo. The death rates of buffalo macrophages were significantly (p<0.05) higher than those of cattle at 60 min and 120 min post-exposure.ConclusionWith higher bacteria killing ability and lower macrophage death, cattle appeared to be more efficient at handling P. multocida B:2 infection than buffalo.