Inflammatory bowel diseases (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are chronic immune-mediated diseases of the gut. Here, the potential role of mast cells (MC) is discussed, mainly focusing on preclinical studies. MC can be activated by antigen-mediated crosslinking of immunoglobulin receptors, by free light chains of immunoglobulins, stress and ATP. Upon activation, MC release bioactive mediators, of which the serine proteases mMCP-6 and Prss31 were shown to be involved in the development of acute colitis. Inhibition of MCs by activation of the inhibitory receptor LIMR3 or inhibitors of proteases may therefore represent new therapeutic targets to treat IBD. Human data are however lacking.