Background: Cutaneous leishmaniasis (CL) is an important tropical neglected disease with broad geographical dispersion. The lack of effective drugs has raised an urgent need to improve CL treatment, and antimicrobial photodynamic therapy (APDT) has been investigated as a new strategy to face it with positive outcomes. Natural compounds have emerged as promising photosensitizers (PSs), but their use in vivo remains unexplored. Purpose: In this work, we investigated the potential of three natural anthraquinones (AQs) on CL induced by Leishmania amazonensis in BALB/c mice. Study Design/Methods: : Animals were infected and randomly divided into four groups: CG (control, non-treated group), G5ClSor-gL (treated with 5-chlorosoranjidiol and green LED, 520??10 nm), GSor-bL and GBisor-bL (treated with soranjidiol and bisoranjidiol, respectively, exposed to violet-blue LED, 410??10 nm). All AQs were assayed at 10 ??M and LEDs delivered a radiant exposure of 45 J/cm2 with an irradiance of 50 mW/cm2 . We assessed the parasite burden in real time for three consecutive days. Lesion evolution and pain score were assessed over 3 weeks after a single APDT session. Results: G5ClSor-gL was able to sustain low levels of parasite burden over time. Besides, GSor-bL showed a smaller lesion area than the control group, inhibiting the disease progression. Conclusion: Taken together, our data demonstrate that monoAQs are promising compounds for pursuing the best protocol for treating CL and helping to face this serious health problem. Studies involving host-pathogen interaction as well as monoAQ-mediated PDT immune response are also encouraged.Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico (CNPq)Fondo para la Investigacion Cientifica y Tecnologica (FONCYT)Secretaria de Ciencia y Tecnologia (SECYT)CNPq: 465763/2014-6FONCYT: 1697; 285/17SECYT: 366/16; 113/17