To observe the effect of moxibustion of "Zhongwan" (CV12) and "Zusanli" (ST36) on histopathological changes of the gastric mucosa and contents of corticotropin-releasing hormone(CRH) and adrenocorticotrophic hormone(ACTH) in the serum, hypothalamus and pituitary tissues in rats with stress-induced gastric ulcer(SGU), so as to reveal its mechanisms underlying improvement of SGU.A total of 28 male SD rats were randomly divided into blank control, model, moxibustion, and medication groups, with 7 rats in each group. The SGU model was established by water immersion restraint stress for 3 h. Moxibustion was applied to "Zhongwan"(CV12) and bilateral "Zusanli" (ST36) for 20 min, once a day for 5 days, and rats of the medication group were treated by gavage of Omeprazole enteric-coated tablets (0.2 mg/kg) once a day for 5 days. The gastric mucosal damage index (ulcer index, UI) was measured to assess the injury severity according to Guth's me-thods. Histopathological changes of the gastric mucosa were determined by H．E. staining. The contents of CRH in serum and hypothalamus and ACTH in serum and pituitary gland tissue were assayed by using ELISA.Outcomes of H．E. staining showed gastric mucosal epithelia defect, disordered arrangement of glands, obvious mucosal hyperemia and edema, exudation of a large number of red blood cells, swelling of mucosal cells with necrosis of nuclei in the model group. These situations were relatively milder in the moxibustion and medication groups. After modeling, the UI, and the contents of CRH in the serum and hypotha-lamus, and ACTH in the serum and pituitary tissue were significantly increased in comparison with the blank control group (<0.01). Following the intervention, the UI, and contents of CRH in the serum and hypothalamus, and ACTH in the serum and pituitary were all down-regulated in both medication and moxibustion groups relevant to the model group (<0.05, <0.01). The therapeutic effect of moxibustion was notably superior to that of medication in down-regulating serum CRH and ACTH (<0.05). No significant differences were found between the medication and moxibustin interventions in lowering the UI, hypothalamic CRH and pituitary ACTH levels (>0.05)．.Moxibustion can relieve gastric mucosal injury induced by stress in water immersion restraint stress rats, which may be associated with its effects in down-regulating the levels of CRH and ACTH in se-rum, hypothalamus and pituitary tissues (inhibition of activities of hypothalamic-pituitary-adrenocortical axis)．.