Hepatocyte growth factor (HGF) is a paracrine multifunctional pleiotropic cytokine. HGF has demonstrated potent anti-inflammatory activity in several animal models of disease and multiple organ systems. HGF suppresses inflammation by targeting multiple pathophysiological processes involved in inflammatory response, including activation of parenchymal cells, microvascular endothelial dysfunction, and leukocyte extravasation and chemotaxis. Mechanistically, this anti-inflammatory action functions by intercepting NFkappaB signaling and subsequently disrupting the expression of NFkappaB-dependent proinflammatory mediators. Thus, HGF might represent a novel integrated multiple-target approach to suppress inflammation and to lower the risk of complications from inflammatory injury.