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The rapid repair of gastric mucosa is critical upon exposure to injurious agents.Intestinal trefoil factor (ITF) is a member of the trefoil factor family (TFF)-domain peptides, which play an important role in the cytoprotection of gastric epithelium.However, the underlying molecular mechanisms that are responsible for ITF-induced gastric epithelial repair remain unclear.In the present study, we demonstrate that ITF enhances the proliferation and migration of GES-1 gastric endothelial cells in a dose and time-dependent manner through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2).Furthermore, the ITF-mediated protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was dependent on the ERK1/2 signaling pathway.Taken together, the results provide a mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa cells, suggesting that activation of the ERK1/2 signaling pathway may provide a new therapeutic strategy for repairing gastric injury.