Leishmania are protozoa that invade mononuclear phagocytes with the involvement of different ligand-receptor systems, including mannose receptors. Until now, scant data are available concerning the mechanisms that govern the infection of Leishmania in other host cell types such as fibroblasts. Our aim was to analyze the expression of mannose receptors in primary cultures of skin fibroblasts (SF) further characterizing their role during the invasion of promastigotes of Leishmania ( L .) amazonensis . Both fluorescent, light, and electron microscopy assays revealed that SF have mannose receptors since they bound and internalized mannosylated ligands in addition to being positively labeled by fuc-BSA-FITC probes. D -mannose competition assays revealed the participation of mannose receptors during the parasite association with SF presenting upregulated receptor expression during the initial steps of the infection. After longer periods of Leishmania :fibroblasts contact, the modulation noted in the host mannose receptors was reverted concomitantly to the infection control, suggesting that the parasites were required for the alteration maintenance and providing evidences that the SF may display microbicidal mechanisms to control the Leishmania infection.