Extracorporeal Shock Wave Therapy (ESWT) is broadly used as a non-surgical therapy in various diseases for its pro-angiogenic and anti-inflammatory effects. However, the molecular mechanisms translating tissue exposure to shock waves (SW) in a biological response with potential therapeutic activity are largely unknown. As macrophages take part in both the onset and amplification of the inflammatory response, and well in its resolution, we investigated the effect of SW on their biology.