In vivo bioluminescence imaging (BLI) methods enable the longitudinal and semi-quantitative monitoring of viral replication dynamics in small animal models and, thus, are useful for examining viral pathogenesis and the effect of antiviral drugs. Here, we describe an in vivo BLI method to evaluate the efficacy of antiviral drugs against rabies virus (RABV) infection in mice. We exemplify mice inoculated with recombinant RABV expressing red firefly luciferase and administered orally with the antiviral drug, favipiravir. For the imaging, mice are intraperitoneally administered with D-luciferin and placed in the dark chamber of an imaging system. The BL images are captured using a highly sensitive charge-coupled device camera. Image data are processed and analyzed using image analysis software.