In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after stimulation of the non-specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0.02) or vaccinated with P. aeruginosa sonicate (p = 0.03) as compared to controls. The histopathology of the surviving rats showed an acute inflammation dominated by polymorphonuclear leukocytes (PMNs), but the offending bacteria were not completely eliminated in any group. The increased survival was probably due to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria.