On the basis of the compound factors of clinical practice, some progress has been made in acute exacerbation models of respiratory diseases by the two-hit method. In this review, we summarize the current research on acute exacerbation models of pulmonary fibrosis, chronic obstructive pulmonary disease, and bronchial asthma established by compound factors. The characteristics and application scope of each model are compared and analyzed in terms of animal selection, model preparation method, and major histopathological changes, providing a reference for researchers to further improve and perfect the model or rationally select animal models.