Objective: To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor (EGFR), phosphorylation extracellular signal-regulated kinase I/2 (p-ERKI/2) and activated protein-1 (AP-2), the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa. Methods: Thirty Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion a/t Zusanli (ST 36) and Zhongwan (CV 12), or Pishu (BL 20) and Weishu (BL 22), once a day, for a total of 8 d. Histolo^cal changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERKI/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-I were measured by Western blots. Results: Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group (P〈0.01, P〈O.05, P〈0.05). Compared with rats in the model group, gastric mucosal damage was milder, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the moxibustion group (all P〈0.01). Conclusion: Moxibustion at Zusanli (ST 36), Zhongwan (CV 12), Pishu (BL 20) and Weishu (BL 21) could increase EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and p