Involvement of mitogen-activated protein (MAPK) in inflammatory bowel disease (IBD) remains enigmatic. We sought to evaluate the expression and activity of p38 and JNK MAPK in IBD and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and the effects of a p38 inhibitor, SB203580, in TNBS colitis. P 38 and JNK were quantified in colonic mucosa of 28 IBD patients and 19 controls and in 77 TNBS or control mice treated or not with SB203580. Colitis severity was assessed by survival, macroscopic and microscopic scoring, and molecular markers. Expression and activity of p38 and JNK were similar in IBD patients and controls and not modified by inflammation. In mice, p38 and JNK expression or activity did not increase following the induction of colitis. SB203580 decreased the p38 activity but displayed no clinical nor biological therapeutic effect. In conclusion, these results minimize the role of p38 and JNK in inflammatory colitis and the interest of p38 as a therapeutic target in IBD.