Lung infections caused by Pseudomonas aeruginosa in cystic fibrosis (CF) patients cause progressive airway obstruction and tissue damage, which is the predominant cause of morbidity and mortality in patients with CF. This paper describes the functional characterization of the pfm gene (open reading frame PA2950) of P. aeruginosa. Using DNA microarrays, we found that the transcriptional levels of type II secretory system genes were significantly reduced in the pfm mutant strain. The type-II-dependent exoprotein LasB could not be secreted normally. The pfm gene was identified as a gene involved in bacterial protein secretion that was critical for the extracellular release of elastase in P. aeruginosa. The abilities to induce lung injury by wild-type and pfm mutant P. aeruginosa were evaluated in a murine acute lung infection model. The results showed that the pathogenicity and virulence of the pfm mutant strain was significantly reduced compared with that of the wild-type strain. The pfm gene and its expression product, as potential new drug targets against P. aeruginosa infection, have important research significance.