When infection occurs, neutrophils rapidly migrate to the affected site. Although the neutrophils neutralize microorganisms, they can also cause tissue damage or render invasion pathways to pathogens. Thus, the migration could be either beneficial or unfavorable in the initial control of infection. Studies on neutrophil recruitment revealed its complexity, especially in terms of the regulation of its initiation. Galectin-3 is a member of the galectin family that has an affinity for β-galactoside containing glycoconjugates. In this study, we investigated the role of galectin-3 in neutrophil migration and the biological significance of the rapid migration of neutrophils in an experimental parasitic cutaneous infection with Leishmania major. When the substrain of L. major, LV39, was infected, lack of galectin-3 impaired neutrophil recruitment in the footpads and the draining lymph nodes 1 d following infection. Reduced number of recruited neutrophils correlated with local high parasite burdens. In contrast, neutrophil migration, induced by the other L. major substrain, Friedlin, was unaffected, and the initial parasite burden remained similar in galectin-3 null mice as compared with wild-type mice. Infection with L. major LV39 but not Friedlin induced higher levels of extracellular release of galectin-3. Further, galectin-3 alone was able to initiate neutrophil migration even though galectin-3 is not a chemoattractant for neutrophils. Thus, our data suggest that once extracellularly released, galectin-3 can act as a damage-associated molecular pattern to facilitate early neutrophil migration, which is beneficial in the initial control of the Leishmania infection.