Membrane type‐1 matrix metalloproteinase (MT1‐MMP) is a proinvasive protease that regulates various cellular functions as evidenced by myriad defects in different types of cells and tissues in MT1‐MMP‐deficient (MT1^−/–) mice. Here we demonstrate that MT1^−/– mice exhibit fewer infiltrating macrophages into sites of inflammation. MT1^−/–macrophages exhibited a reduced ability to invade reconstituted basement membrane (Matrigel) and invasion by wild type (WT) macrophages was inhibited by a synthetic MMP inhibitor (BB94) to a level similar to that of MT1^−/– cells. The rate of migration of MT1^−/– macrophages was also low compared to that of the WT cells and re‐expression of MT1‐MMP in MT1^−/– macrophages reconstituted their migratory activity. Unexpectedly, however, BB94 did not inhibit the migration of WT macrophages. The migration‐boosting activity of MT1‐MMP is retained in a mutant that lacks most of the extracellular portion including the catalytic and hemopexin‐like domains. In contrast, deletion of the cytoplasmic (CP) tail abolished the activity completely. Thus, we have demonstrated that MT1‐MMP regulates macrophages via its invasion‐promoting protease activity as well as its CP‐dependent non‐proteolytic activity to boost cell migration.