Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In the last years, silver nanoparticles have appeared as novel antimicrobial agents. In this work, we evaluated the therapeutic potential of silver nanoparticles prepared by two different processes: 1) chemical synthesis (Chem-AgNP); and 2) biosynthesis from the fungus Fusarium oxysporum (Bio-AgNP), in the treatment of cutaneous leishmaniasis. When tested in vitro against Leishmania amazonensis promastigotes, Bio-AgNP was 4-fold more potent than Chem-AgNP (IC50 = 25 uM and 100 uM, respectively). In vivo studies in mice infected in the ear showed that bi-weekly intralesional injections with only 6.5 ug/Kg of body weight of Bio-AgNP during 4 weeks were equally effective as 300-fold higher doses of the reference drug amphotericin B, and more effective than 3-fold higher doses of Chem-AgNP. Contrary to the hepato- and nephrotoxicity that resulted from amphotericin B treatment, and the slight hepatotoxicity produced by Chem-AgNP, no changes in serum levels of AST, ALT and creatinine were detected with Bio-AgNP. Together, these findings show that the biogenic synthesis resulted in enhanced in vitro and in vivo antileishmanial activities, and safer silver nanoparticles as compared with the chemical synthesis.208997Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)