INTRODUCTION: Recent clinical trials show Lactobacillus rhamnosus GG (LGG) administration in critical illness has the potential to reduce nosocomial infections and improve clinical outcome. However, the mechanism(s) of LGG-mediated benefit following illness and injury remain elusive. OBJECTIVE: The aim of this study was to determine the effect of LGG treatment on survival and lung injury in a mouse model of Pseudomonas aeruginosa-induced pneumonia. As increased T regulatory (Treg) cell numbers have been shown to improve outcome in experimental pneumonia, we examined the potential role of Treg cells in probiotic-mediated benefit. METHODS: FVB/N mice were subjected to intratracheal injection of either P. aeruginosa or saline and received LGG or vehicle immediately before procedure. T regulatory cell responses in the lung were evaluated by polymerase chain reaction, Western blotting, and flow cytometry. RESULTS: Mice treated with LGG had significantly improved 7-day survival (P < 0.01) compared with saline-treated control pneumonia mice (55% LGG vs. 14% control). The survival advantage was associated with reduced bacterial counts in bronchoalveolar lavage and with decreased markers of the systemic inflammatory response and improved lung pathology in the probiotic group. Probiotic treatment influenced immune response in the lungs of mice with pneumonia as demonstrated by increased levels of Treg cell marker Foxp3. CONCLUSIONS: These data demonstrate that early administration of LGG improves outcome following P. aeruginosa-induced pneumonia. An effect of LGG on Treg cells may play a role in this protection.