Pasteurella pneumotropica, a gram negative opportunistic pathogen, can be isolated from the oropharynx and the intestinal tract of normal mice and has been associated with various clinical syndromes including conjunctivitis, infections of the reproductive tract, otitis, and subcutaneous abscess formation. Enrofloxacin a fluoroquinolone bacteriocidal antimicrobial, has been shown to be effective in eliminating Pasteurella multocida from rabbits. We sought to determine whether enrofloxacin would eliminate P. pneumotropica from mice known to be asymptomatically infected with the agent. P. pneumotropica-positive (culture and immunofluorescence assay) male (n=55) and female (n=55) C57BL/6N mice were randomly assigned to 1 of 7 treatment groups or to a control group. These groups were designed to evaluate the efficacy of enrofloxacin at three different dose levels (8.5, 25.5, and 85.5 mg/kg/day) over a 14 day treatment period via oral administration in the drinking water or via parenteral injection. A tetracycline-treated (60mg/kg/day) and an untreated control group were included for comparisons. Repeated oropharyngeal and fecal cultures through 30 days post-treatment, and samples from numerous enteric and reproductive organs collected during necropsy, were used to evaluate group differences. Enrofloxacin eliminated evidence of P. Pneumotropica from all sites sampled when administered at either 25.5 or 85 mg/kg, but not at 8.5 mg/kg, by either route for at least 30 days post-treatment. Tetracycline and control groups remained consistently culture positive throughout the study. We concluded that the oral route may be a more practical method for treating large numbers of mice. Also, enrofloxacin may be a practical and inexpensive alternative to caesarian rederivation or embryo transfer for the elimination of P. Pneumotropica in mice. Ongoing research in this area includes further refinement and optimization of the enrofloxacin treatment dose and duration and evaluation of its efficacy under less stringent husbandry conditions.