Neuropathic pain affects millions of people globally and could be a disease on its own right. Current treatments focus on blocking neurotransmission and have resulted in limited success. Recent progress points to an important role of neuroinflammation in the pathogenesis of neuropathic pain. Matrix metalloproteases (MMPs) comprise a large family of zinc endopeptidases that have been implicated in the generation of neuroinflammation via cleavage of extracellular matrix proteins and activation of proinflammatory cytokines and chemokines. However, little is known about the role of MMPs in chronic pain regulation. Our recent study has shown that neuropathic pain development in the early and late phase requires MMP-9 and MMP-2, respectively. Inhibition of MMP-9 or MMP-2 might provide a new strategy for the prevention and treatment of neuropathic pain.