Diabetes mellitus (DM) is a chronic disease characterized by high blood sugar levels. Currently, due to genetic characteristics, a poor eating habits and a sedentary lifestyle, about 90-95% of diabetes cases are type 2, characterized by peripheral insulin resistance. DM increases the risk of extracellular bacterial infections and fungal infections, and changes the clinical presentation and response to treatment of these infections. The cutaneous leishmaniasis (CL) is a disease that predominantly affects adults, young males, but the number of children and the elderly with the disease has increased in recent years. The study included 36 DM patients with CL and 36 patients with CL without DM aged 18 to 60 years who sought the reference center of Corte de Pedra from January 2017 to June 2020. The diagnosis of CL was performed by detection of L. braziliensis DNA in tissue biopsies. DM was diagnosed when glycated hemoglobin was ≥6,5. Mononuclear cells of the peripheral blood were stimulated with soluble leishmania antigen and cytokines were measured in supernatants by ELISA. A lesion biopsy was also performed for histopathological and immunohistochemical studies. All patients were treated with Glucantime® (Sanofi-Aventis) at a dose of 20mg/kg/day. The cure was defined by the complete healing of the ulcers on day 90 in the absence of elevated borders. There was no difference between the 2 groups in relation to the duration of the disease, location and size of the lesion. There was no difference in the frequency of cells expressing CD20 + (lymphocyte B) and CD68 + (macrophages), however, there was a decrease in the frequency of CD8 + cells in patients with CL with DM. The most important clinical difference between the 2 groups was the presence of atypical lesions characterized by superficial ulcers without well-defined borders in 13 (36%) of the diabetic patients. Moreover, while there was no difference in the cure rate in DM + CL (67%) and in CL without DM (56%), P>0.05, the cure rate in diabetes with atypical lesions was 31% and in those with typical lesions was 87%, P<0.01. The production of IFN-γ, TNF, and IL-1β was higher in patients with atypical lesions than in patients with typical lesions. The most important finding herein was documentation of the capability of DM to modify the clinical presentation of CL, due to the appearance of atypical CL lesions associated with a poor response to therapy. In our study, the atypical lesions observed were predominantly flat, usually large, and lacked well-defined borders. While more superficial ulcers may occur due to a lower frequency of cytotoxic CD8+ T cells at the lesion site and decreased necrosis, the high rate of failure of therapy seen in these patients may be occurring due to an increase in the synthesis of proinflammatory cytokines. Conclusions: There was no evidence that sugar blood levels influenced the presentation and response to therapy of CL. However diabetic patients who had an exaggerated inflammatory response had atypical lesions and more failure to therapy.