Objective To establish and evaluate a mouse model of inhaled anthrax infection by Bacillus anthracis(Pasteur II strain) spores by aerosolized intratracheal inoculation. Methods B10. D2-Hc0H2d H2-T18c / oSnJ mice lacking complement component C5 were infected with Bacillus anthracis Pasteur II strain spores (attenuated strain) by aerosolized intratracheal inoculation. Disease progression, tissue bacterial load, histopathological changes, cytokine response, and acute reactive protein levels were examined after infection. Results The median lethal dose was 5×103 CFU. Multiple organ metastasis and bacteremia occurred within 12 hours after pulmonary infection of anthrax spores. Histopathological changes and inflammatory responses were similar to those in other species including rabbits, nonhuman primates, and humans. C-reactive protein and amyloid protein P levels in serum and alveolar lavage fluid indicated that acute inflammatory responses were triggered after infection. Conclusions This model can be used as an alternative small animal model to further elucidate the pathogenesis of Bacillus anthracis and differences in host susceptibility to B. anthracis, providing new approaches for anthrax vaccines and therapeutic drug development.