The lesion infiltrate from the ulcerated phase of CL is predominantly composed by lymphocytes, NK cells and macrophages, and few parasites are observed. In this phase of the disease strong inflammatory response, with high levels of TNF and IL-important role for CD8+ T and NK cells in the pathogenesis of CL has been documented. We have shown that these cells produce high amounts of granzyme B, enhancing pro-inflammatory responses at lesion site. Before the ulcer develops, CL individuals present appearance of an exoulcerative papule. Patients in this initial phase of the disease have higher parasite load and higher rate of therapeutic failure when compared to ulcerated CL individuals. To investigate the immune response at lesion site in the initial phase of the disease, we cultured lesion fragments from CL patients in the initial and ulcerated phase of the disease. We observed that CL patients in the initial phase of the disease produce high levels of angiogenesis-related factors, NK cells activation factors (IL-2 and IL-15) factors (CXCL9 and CXCL10). CXCL10). Addition of exogenous IL-10 to lesions cells from CL patients in the initial phase of the disease was only able to decrease the production of IL-2 and TNF. Signaling through PPAR-gamma, a nuclear lipid receptor, often leads to anti-inflammatory and wound healing responses. Addition of Omega 3, a PPAR-gamma ligand, to Leishmania antigen-stimulated PBMC decreased proinflammatory cytokines and increased parasite killing. Our data suggest that increased production granzyme B, CXCL9 and CXCL10 is associated with ulcer development in CL patients and show that cells infiltrating the lesion site are mostly unresponsive to IL-10. Furthermore, signaling through PPRA-gamma might benefit patients, decreasing inflammatory response and enhancing parasite killing.