Membrane type 1 (MT1)-MMP is a member of matrix metalloproteinases (MMPs) that regulates extracellular matrix remodeling. In addition, MT1-MMP also serves as a multi-functional protein. However, the functional role of MT1-MMP in human endothelial cells remains unclear. In this study we use real-time PCR and Western blotting to demonstrate for the first time that MMP-2 expression is regulated by MT1-MMP in human endothelial cells. Moreover, MMP-2 activity is also modulated by MT1-MMP. In addition we found that endothelial cells, ECM adhesion and human endothelial cell tube formation, which are known to be regulated by MMP-2, are blocked by MT1-MMP siRNA. These results suggest that MT1-MMP plays an important role in regulating angiogenesis in human endothelial cells. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.