OBJECTIVE: Restraint water-immersion stress (RWIS) can induce a gastric mucosal lesion. Our objective was to detect the phenotype of activated neurons in the medulla oblongata of rats subjected to RWIS. STUDY DESIGN: Male Wistar rats were divided into 2 groups in accordance with the duration of RWIS: a control group and the RWIS group. The brain sections were treated with a dual immunohistochemistry of Fos and choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) or oxytocin receptor (OTR) or vasopressin 1b receptor (V1bR) or methionine-enkephalin (M-ENK). RESULTS: Compared to the control group, the number of Fos+ChAT-immunoreactivity (IR) neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguous (NA) and that of Fos+TH-IR neurons in the nucleus of the solitary tract (NTS) were evidently increased in the RWIS group; meanwhile, more OTR-IR and V1bR-IR neurons in the DMV and NTS were activated. A few M-ENK-IR perikarya were observed only in the NTS, with no difference between the RWIS and control groups. CONCLUSION: Data suggest that the hyperactivity of cholinergic neurons in the DMV and NA and catecholamine neurons in the NTS is one of the main mechanisms of gastric mucosal lesions induced by RWIS; the OT-sensitive and AVP-sensitive neurons, excepting M-ENK ones, are involved in the modulation of the gastric mucosal lesion during RWIS. © Science Printers and Publishers, Inc.