With the acceleration of urbanization and aging and the change of lifestyle, inflammatory diseases have become one of the important threats to the health of the global population. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the metabolism of extracellular matrix (ECM). They play a key role in inflammation-related diseases. Factors such as inflammation, oxidative stress and growth factors stimulate the production of MMPs with subsequent ECM remodeling. Recently, the studies of epigenetic regulation, including the ability to predict disease progression, important pathophysiological deficiencies as well as treatment methods have been extensively discussed. This article reviews the current studies on epigenetic alterations in MMPs during inflammatory response. It is likely to provide new insights into development of efficient medications of epigenetic therapy for inflammatory diseases.