Acute lung injury (ALI) models are characterized by neutrophil accumulation, tissue damage, alteration of the alveolar capillary membrane, and physiological dysfunction. Lipoxin A(4)(LXA(4)) is an anti-inflammatory eicosanoid that was demonstrated to attenuate lipopolysaccharide-induced ALI. Experimental models of severe malaria can be associated with lung injury. However, to date, a putative effect of LXA(4)on malaria (M)-induced ALI has not been addressed. In this study, we evaluated whether LXA(4) exerts an effect on M-ALI. Male C57BL/6 mice were randomly assigned to the following five groups: noninfected; saline-treatedPlasmodium berghei-infected; LXA(4)-pretreated P. berghei-infected (LXA(4)administered 1 h before infection and daily, from days 0 to 5 postinfection),LXA(4)- and LXA(4) receptor antagonist BOC-2-pretreated P. berghei-infected; and LXA(4)-posttreatedP. berghei-infected (LXA(4)administered from days 3 to 5 postinfection).By day 6, pretreatment or posttreatment with LXA(4)ameliorate lung mechanic dysfunction reduced alveolar collapse, thickening and interstitial edema;impaired neutrophil accumulation in the pulmonary tissue and blood;and reduced the systemic production of CXCL1.Additionally,in vitro treatment with LXA(4) prevented neutrophils from migrating toward plasma collected fromP. berghei-infected mice. LXA(4)also impaired neutrophil cytoskeleton remodeling by inhibiting F-actin polarization. Ex vivoanalysis showed that neutrophils from pretreated and posttreated mice were unable to migrate. In conclusion, we demonstrated that LXA(4)exerted therapeutic effects in malaria-induced ALI by inhibiting lung dysfunction, tissue injury, and neutrophil accumulation in lung as well as in peripheral blood. Furthermore, LXA(4) impaired the migratory ability of P. berghei-infected mice neutrophils.