Influenza virus infection is a zoonosis that results in high mortality in animals and humans. Several recent avian influenza outbreaks have posed a significant public health threat to humans because there have been many cases of direct interspecies transmission from birds to humans. Influenza virus infection causes acute respiratory failure, which is the main cause of death, while chronic influenza virus infection in the central nervous system results in neural dysfunction. Of particular interest, according to one report, a group of patients who recovered from influenza virus infection during pandemics showed neuropsychiatric disorders, including depression, schizophrenia, and Parkinsonism. Thus, study of the etiology of neuropsychiatric disorders caused by influenza virus infection is needed. In order to conduct necessary experiments, it is essential to reproduce neurological phenomena that are manifested by human patients who have recovered from influenza virus infection using laboratory animals. In this review, we will discuss some of the facts that should be considered when establishing an animal model for study of central nervous system responses to influenza virus infection using mice.