Clinically,flaviviruses can cause central nervous system (CNS) diseases and easily cause sequelae of the nervous system. Flaviviruses can enter the brain through blood-borne pathways,Trojan horse pathways,and axon transport,ultimately leading to CNS infection. When the virus enters the CNS through BBB,glial cells and nerve cells activated by the virus will release a large number of inflammatory mediators and up-regulate the expression of adhesion molecules,recruiting leukocytes to the CNS. Leukocyte infiltration can carry more viruses into the CNS and destroy the integrity of the BBB. It is generally believed that the inflammatory factors produced by glial cells and nerve cells are the main cause of increased BBB permeability. This review will focus on the research progresses of the BBB damage and the CNS invasion to better understand of pathogenesis and effectively prevent the spreading of flaviviruses.