Introduction: Several investigations revealed that the activation of the innate immune system plays a crucial role in the pathogenesis of numerous diseases. The innate immune system activation occurs in response to pathogens or tissue injury via pattern-recognition receptors that recognize pathogen-associated molecular patterns. The innate immune system triggered by these interactions besides the general responses causes a specific response to pathogen. In addition, this pathogen-specific innate response affects the specificity of the adaptive immune response through directing the differentiation of T-cells into functionally distinct subtypes. Although the mechanism(s) by which different Rabies viruses induce differential immune responses are unknown, recent studies indicate that the consequence of rabies virus infection is dependent upon the rapid stimulation of innate and adaptive immunity. The responses prevent viral entry into the central nervous system (CNS), where it can escape immunity. Laboratory strains that reach the CNS can be cleared and this has obviously happened in individuals with rabies. Thus, during rabies virus infection, pattern-recognition receptors of rabies can be recognized in the periphery and the CNS. Conclusion: To study these possibilities, the consequence of rabies infection in mice lacking adaptor myeloid differentiation factor 88 (MyD88) was demonstrated. Toll-like receptors (TLRs) signals, except for TLR3, activate proinflammatory reaction via the adaptor protein MYD88. Only mice lacking TLR7 displayed a marked mortality compared with MyD88 negative and control mice with deficits in both the development of peripheral immunity and rabies virus clearance from the CNS. The review demonstrated that TLR7 plays a vital role in controlling and directing of immune response against the rabies virus.