Following severe burn injury, persistent inflammation perpetuated by surface eschar, bacterial colonisation and neutrophil proteolytic activity can impede normal healing and result in further tissue damage. Extracorporeal shock wave treatment (ESWT) has been shown in the clinical setting to promote the healing of burn and difficult-to-heal wounds; however, the mechanism is unclear. We investigated the role of ESWT on the early proinflammatory response using a severe, full-thickness and highly inflammatory cutaneous burn wound in a murine model. Various wound-healing parameters were measured and leukocyte infiltration quantitated. A panel of 188 candidate genes known to be involved in acute inflammation and wound healing was screened. We show that ESWT of burn wounds 1 hour postwounding significantly blunts polymorphonuclear neutrophil and macrophage infiltration into the wound. ESWT treatment potently attenuates both CC- and CXC-chemokine expression, acute proinflammatory cytokine expression and extracellular matrix proteolytic activity at the wound margin. Given these findings and the clinical success of ESWT, we speculate that ESWT may be a potential therapeutic modality to treat severe wounds wherein excessive inflammatory responses involving increased levels of inflammatory cells, proinflammatory cytokines and proteases may become self-resolving allowing wound healing to progresses by way of normal physiological repair processes.