Actinobacillus pleuropneumoniae is a Gram-negative pathogen. It is the aetiological agent of porcine contagious pleuropneumonia (PCP), a severe and highly contagious and severe respiratory disease of swine. Four sets of RTX (repeats in toxin) exotoxins have been described in A. pleuropnuemoniae and three of them have been characterized as important virulence determinants. The aim of this study was to determine the pathogenicity of the invivo induced RTX toxin ApxIVA during infection of piglets with A. pleuropnuemoniae. An A. pleuropnuemoniae apxIVA mutant was obtained based on an A. pleuropnuemoniae apxIIC-deleted mutant strain. An experimental infection assay was performed to evaluate the virulence of ApxIVA in piglets. Clinical signs, lung lesion scores, blood biochemical parameters and histopathologic changes in the piglets were recorded. The results indicated that the pathogenicity of A. pleuropnuemoniae was greater when ApxIVA was present, suggesting that ApxIVA is essential for expression of the full virulence of A. pleuropnuemoniae.