Actinobacillus pleuropneumoniae (App) is the etiological agent of porcine pleuropneumonia which causes huge economic losses to the pig industry. RTX (repeat in the structural toxin, RTX) is the main virulence-associated factor of the pathogen and, plays a dual role on the pathogen's infection and immunity. Recently research progress is updated in this paper and the necessity and techniques to initiate the pathogen-host interaction study is also raised and discussed. It is believed that the research on the interaction between host and App RTX may further elucidate the pathogen' s molecular pathogenesis.