Lung transplantation is the only conclusive treatment for many patients suffering from end-stage pulmonary disease. Unfortunately, the leading cause of death in lung transplant recipients is the development of chronic rejection known as obliterative bronchiolitis, characterized by extensive remodeling. Matrix metalloproteinases (MMPs) are endopeptidases known for their role in matrix remodeling and their involvement in many biological processes including end-stage pulmonary disease and transplant rejection. Our understanding of MMPs involvement in pulmonary immunity is rapidly expanding. As a result there has been some focus on MMPs role in T cell-associated pulmonary diseases, such as pulmonary fibrosis, emphysema, asthma and bronchiolitis obliterans syndrome. However, not much is known about the role of MMPs in regulating immune cell function. It is now commonly known that MMP inhibition via, broad spectrum or specific synthetic or naturally occurring inhibitors (TIMPs) can down regulated many pulmonary disease states. In this review, we explore the idea that T cell targeted MMP inhibition may provide a novel approach of immune regulation in the treatment of T cell-mediated diseases.