ObjectiveTo investigate the role of p38 MAPK on gastric ischemia/reperfusion (I/R)induced injury in mice.MethodsC57BL/6 mice were randomly divided into three groups: sham+vehicle group, I/R+vehicle group (as control), and I/R+CNI1493 group. The gastric IR injury mice were prepared by occluding the celiac artery for 30 min followed by reperfusion for 1 h. Shamoperated animals underwent the same surgical procedure without clamping. Physiological saline (0.9% NaCl, 10 ml/kg) or CNI1493(a p38 MAPK inhibitor, 10 ml/kg, 2 mg/ml) was intraperitoneally administered 1 h before ischemia. A picture of the whole stomach was obtained after fixation with formalin, and the bleeding area in the whole stomach was obtained by a digital imaging analyzer (Image J 1.4. NIH). The levels of phospho and totalmitogenactivated protein kinases (MAPKs including p38, JNK, and ERK), phosphonuclear factorκB (NFκB) and cleaved Caspase3 in the injured stomach tissue were determined by Western blotting analysis.ResultsCompared with sham+vehicle group, I/R group had markedly larger gastric bleeding area (P<0.05), activated p38, JNK, and ERK (P<0.05), and markedly increased NFκB p65 and cleaved Caspase3 expression (P<0.05). Pretreatment with CNI1493 significantly inhibited the above changes in I/R group (P<0.05). ConclusionActivation of MAPK/NFκB pathway play a very important role in I/Rinduced gastric injury. Pretreatment with p38 MAPK inhibitor, CNI1493, can inhibit MAPK/NFκB pathway, decrease expression of apoptosis protein expression, and reduce gastric mucosal bleeding.