Long pentraxin 3 (PTX3) is a newly discovered acute phase protein produced at the sites of infection and inflammation by tissue cells, macrophages, monocytes, and dendritic cells. PTX3 plays an important role in preventing infection of certain fungi, bacteria, and viruses in the lung. Recombinant PTX3 has been proposed as a potential antifungal molecule for therapy. However, under certain experimental conditions, such as intestinal ischemia-reperfusion, high volume mechanical ventilation, or severe bacterial infection, increased expression of PTX3 is associated with more severe lung injury. Therefore, it is necessary to further explore the sources of PTX3 in the lung and the regulatory mechanisms of its expression. It is also essential to further determine how PTX3 binds to pathogens, complement, and apoptotic cells, and to determine whether PTX3 has a specific receptor in targeted cells. These studies will provide insight into the pathological processes of pulmonary infection and acute lung injury and provide potential novel therapeutic strategies to control pulmonary infections without severe lung injury.