Molecules from animals or plant species have been investigated with the aim of treating diseases of epidemiological importance, such as rabies, which is a viral, acute, and infectious disease with approximately 100% lethality. Rabies has been one of the main causes of death in humans concerning infectious diseases. This work investigated the action and preliminary mechanisms of the alkaloid bufotenine in an in vivo model with the rabies virus. A wild-type virus was titrated and injected into mice for the determination of DL50 in the presence or absence of bufotenine. The results reveal that bufotenine has possible action in modulating the immune response of the studied host, suggesting interference in delaying symptom manifestation. Regarding the histological analysis of the CNS of the animals, bufotenine possibly prevented the presence of mononuclear cell inflammatory infiltrate in the meninx’s region compared to the positive control and possibly contributed to reducing neuronal degeneration. The use of the bufotenine extracted from the seed of white angico, a plant representative of Brazilian flora, contributed to antiviral activity with effects on the immunological aspects of the host infected by the rabies virus.