Introduction:The treatment of leishmaniasis ischallenging, given the diffi culties in drug administration and resistance. Therefore, we chose to test the effi cacy of miltefosine combined with pentoxifylline. Methods: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/ kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. Results: The number of viable Leishmania reduced signifi cantly within the miltefosine-pentoxifylline group (p < 0.05). Conclusions: There is hope that a viable treatment exists for Leishmania infection.