Proteinases have been shown to act as signaling molecules that are able to send specific signals to cells through the activation of proteinase-activated receptors (PARs). Those receptors which are expressed in a wide variety of cells in the gastrointestinal tract are considered as "emergency" mechanisms, particularly involved in inflammatory responses of the gut. Depending on the cell types of the gut in which PARs are activated, their activation interacts with all aspects of the gut physiology: motility, barrier function, transports, innate immune response, sensory functions, and even proliferation. A growing body of evidences discussed here suggests that these receptors, and the proteinases that activate them, are important mediators of the innate immune response of the gut and could play a major role in chronic inflammatory states of the gut (inflammatory bowel diseases), or infectious diseases.