The extracellular matrix (ECM) generates multiple bioactive fragments, termed matrikines, which play pivotal roles in ECM functions. Acetylated proline-glycine-proline (AcPGP) is a matrikine derived from collagen. By binding to the C-X-C chemokine receptor type 1 and 2, AcPGP exhibits complex biological effects such as inflammatory responses, vascular permeability, tissue repair and remodeling. In the lungs, the dys-regulation of AcPGP contributes to a variety of respiratory diseases, and serves not only as a biomarker for diagnosis and assessment but also as a potential therapeutic target. This article reviews the regulatory mechanisms, biological functions of AcPGP in the lungs, and its role in respiratory diseases such as chronic airway inflammation diseases, acute lung injury, and pulmonary fibrosis.