Introduction Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by the presence of one or more ulcerated lesions with elevated borders. Cellular infiltrate in lesions of these individuals are composed mainly by mononuclear cells, including CD4+, CD8+, plasm cells and cells from myeloid lineage. High levels of IFN- γ and TNF- α are detected in these patients and these proinflammatory cytokines are known to play a role in the pathogenesis of CL, by inducing tissue damage. Upon infection with Leishmania or in presence of soluble Leishmania antigen, monocytes from CL individuals produce high levels of TNF-alpha and chemokines involved in recruitment of CD4+, CD8+ T cells and monocytes. Recent studies have shown that circulating monocytes constitute a heterogeneous population, and based on expression of CD14 and CD16, these cells can be divided in classical (CD14+CD16−), intermediate (CD14+CD16+) and non-classical (CD14−CD16+) monocytes. Intermediate and non-classical monocytes are known to migrate to inflamed sites and secrete inflammatory mediators, and high frequency of these cells has been associated with pathogenesis of many inflammatory diseases. TNF- α can mediate the pathology of the disease through various mechanisms including induction of nitric oxide, apoptosis, expression of metalloproteinases (MMPs) and increased cytotoxicity. MMP-9 is a zinc-dependent enzyme that degrades collagen type 4 (present in basal membrane) and has been associated with skin inflammatory diseases. Although the mechanism underlying ulcer development in CL is not known, it is likely that MMP-9 contribute to tissue damage since it was documented that L. braziliensis -infected macrophages upregulate MMP-9. Methods Peripheral blood mononuclear cells were obtained from patients with cutaneous leishmaniasis and uninfected controls. Cells were analysed ex-vivo or after culture in presence of Leishmania parasites, antigen or LPS, for MHC II, co-stimulatory molecules, TNF-alpha and MMP9. Results Thus, our goal was to investigate the contribution of sub-populations of monocytes to TNF-alpha and MMP-9 secretion in CL patients. We found that early after infection (pre-ulcerative phase) the frequency of intermediate and non-classical monocytes are elevated in blood of CL individuals. Also, while intermediate monocytes produced more TNF-alpha in response to Leishmania , non-classical ones were the main source of MMP-9 in most CL patients. Similarly, the biopsies studies reveled that the non-classical monocytes were the main MMP-9 producing cells. Conclusion These results show that monocytes subpopulations contribute differently to the immunopathology observed in CL patients.