The pathogenesis of porcine contagious pleuropneumonia is poorly understood. In the present study, a mouse model of intranasal infection by Actinobacillus pleuropneumoniae (App) was used to examine lung inflammation. The pathogical results of lung tissues showed that App-infected mice showed dyspnea and anorexia, with severe damage by acute hemorrhage, and infiltration of eosinophils and lymphocytes, as well as increased expression of caspase-1 p20, interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α. Caspase-1 inhibitors reduced both lung tissue damage and the expression of caspase-1 p20, IL-1β, IL-6, IL-8, TNF-α and IL-18 in infected mice. These findings suggest that the caspase-1 dependent pyroptosis involved in the pathogenesis of the mouse pleuropneumonia caused by App and the inhibition of caspase-1 reduced the lung injury of this pleuropneumonia