Bats are important reservoirs of zoonotic viruses, including the rabies virus (RABV), which causes rabies, a significant and fatal disease. In Brazil, RABV has been detected in several bat species. Interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) is part of a group of interferon-stimulated genes (ISGs) known for their antiviral activity. This study investigated the interaction between batIFIT5 and different genetic lineages of RABV. The batIFIT5 was expressed in HEK-293T cells, which were infected with RABV genetic lineages isolated from Eptesicus furinalis (IP 964/06) and Tadarida brasiliensis (IP 3214/19), at varying infectious doses (pure, 100, 10, and 1). Direct immunofluorescence was performed to assess the effect of batIFIT5 on virus replication through the counting of fluorescent foci. Subsequently, after the expression of batIFIT5, 1 MOI was selected and used to evaluate the potential antiviral effect. Immunofluorescence was performed 24 and 48 h after infection. As a result, the viral concentration remained similar in the presence of batIFIT5 across distinct infectious doses. After infection with 1 MOI, a 30% reduction in infection rates was observed, particularly for the IP 3214/19 isolate after 24 h. These results highlight the potential antiviral role of IFIT5 against RABV infection.