The purpose of this study was to characterize the immunopathological response in the skin of S. apella infected with Leishmania (L.) amazonensis and L. (V.) braziliensis parasites, the main causative agents of localized cutaneous leishmaniasis in South America. In infected animals, amastigote forms of L. (L.) amazonensis could be detected till 120 days postinfection (PI), while, in L. (V.) braziliensis infection, parasites could be detected until 180 days PI in the skin sections. CD20(+) cells were detected throughout the experimental time in both groups as well as in CD3(+) cells, which appeared to be activated because high densities of inducible nitric oxide synthase (iNOS(+)) cells were detected at 60 and 90 days PI in both studied groups. After 60 and 120 days PI, decrease in iNOS(+) cells was observed in L. (L.) amazonensis and L. (V.) braziliensis, respectively, which was associated with parasite clearance. Increase in lysozyme(+) cells was observed during the experimental infections, which also can be associated with parasite killing.