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INTRODUCTION: Pseudomonas aeruginosa is a gram-negative rod bacterium known as an important opportunistic human pathogen that causes severe infections in impaired patients. While vaccines could potentially prevent P. aeruginosainfection, none are currently licensed despite decades of intensive research. Thereby, in this study we evaluated the anti-P.aeruginosa IgG response in mice immunized with BSA nanoparticles vaccine associated to total antigens of P. aeruginosa and also the protective potential of this formulation to reduce the inflammatory signs developed after nasal infection by this agent. MATERIALS AND METHODS:Mice were immunized via the subcutaneous route using empty nanoparticle (NPe) or nanoparticle associated to P. aeruginosa antigens (NPPa) on days 0, 7 and 14. The antibody production was measure by ELISA and bacterial agglutination test. Immunized mice were challenged with live P. aeruginosa and the lungs of these mice were collected for histopathology studies. RESULTS: We observed a robust production of anti-P. aeruginosa IgG antibodies in mice immunized with NPPa. The antibodies are functional due to their ability to bind and induce agglutination in live P. aeruginosa cells in vitro. To assess a protective anti-P. aeruginosa immunity, the histological examination of lungs from animals immunized with NPe in all times tested revealed large scattered areas of intense inflammation. It was also verified the presence of dilated and hyperemic vessels, but with mild edema and hemorrhage. The lung sections from animal immunized with NPPa showed a less-extensive microscopic evidence of lung tissue damaged. There was less dilated and hyperemic vessels, less intraalveolar hemorrhage, less alveolar septum wall edema, and a lower inflammatory reaction seen in lung tissues from these animals, either in 1 or 4 days after infection. So, as the NPPa reduce the inflammatory signs in mice, this formulation could be beneficial to cystic fibrosis patients and other pathological conditions involving P. aeruginosa infections.CONCLUSION: The immunization with BSA nanoparticles associated with total antigens of Pseudomonas aeruginosa induces strong humoral responses against the bacteria and also is able to lower the inflammatory signs in lungs caused by nasal infection with this pathogen.