Polyunsaturated fatty acid (PUFA) immunomodulatory properties have been studied extensively in chronic infections. Few studies have focused on acute infection; thus, PUFA effects in a mouse model of Pseudomonas aeruginosa (PA)-induced lung injury were evaluated. C57BL/6 mice were randomized to be fed for 3 wk with an eicosapentaenoic acid (EPA) diet, an arachidonic acid (AA) diet, or a control diet [saturated fatty acids]. Lung injury was induced by intratracheal instillation of 10(7) CFU of PA per mouse. In each diet group, animals were studied either without or after PA-inducing lung injury. Evaluation criteria were early mortality; inflammatory response assessed with tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-10 levels in bronchoalveolar lavage; lung injury evaluation; and extravascular lung water, assessed 24 h after the injury. After PA-induced lung injury, no difference in early mortality was observed; TNF-alpha level was significantly higher in the EPA diet than in the other two diet groups. No difference for the other cytokines was found among the groups. Lung edema was also more important in the EPA group, consistent with the variations of TNF-alpha levels. Our study clearly shows that in PA-induced acute lung injury, n-3 PUFA induces differences in the inflammatory response with a higher level of lung edema. Modulation of the inflammatory response with n-3 PUFA can influence the response to a bacterial challenge.