BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. Tissue therapy has been investigated as a possible therapeutic option for patients with cardiovascular disease. OBJECTIVE: This study evaluated the effects of therapy with mesenchymal stem cells in an experimental model of chronic Chagasic cardiomyopathy. METHODS: C57BL/6 mice were infected with 1000 trypomastigotes from the Colombian strain of T. cruzi and, after six months of infection, were treated with mesenchymal human stem cells from adipose tissue (STAT) or with Dulbecco/Vogt modified Eagle's minimal essential medium - DMEM (control). The treated group received two intraperitoneal injections of STAT (1x10(6) cells/dose), with a month interval between the two doses. Before and after the first and second months of treatment, the chagasic and normal control animals underwent cardiopulmonary exercise testing and electrocardiography. All animals were sacrificed under anesthesia after two months of treatment for histopathological analysis of the heart. RESULTS: No improvement was observed in arrhythmias and cardiovascular function in the group of animals treated with STAT; however, sections of mice hearts in this group revealed a significant reduction in the number of inflammatory cells (p<0.0001) and areas of fibrosis (p<0.01) in comparison with chagasic animals treated with DMEM. CONCLUSION: Thus, it is concluded that administration of intraperitoneal STAT can reduce inflammation and fibrosis in the heart of mice chronically infected with T. cruzi; however, there were no effects on the cardiac function two months after transplantation.