Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. The development of gastric symptoms may depend on how humans adapt to the stressful events in their daily lives. Although acute stress delays gastric emptying and alters upper GI motility in rodents, the effects of chronic stress on gastric motility and its adaptation mechanism remains unclear. Central oxytocin has been shown to have anti-stress effects. We studied whether central oxytocin is involved in mediating the adaptation mechanism following chronic repeated stress. Mice were loaded with acute and chronic stress (repeated stress for 5 consecutive days) and solid gastric emptying and postprandial gastric motility were compared between acute and chronic repeated stress. Expression of oxytocin and corticotropin releasing factor (CRF) mRNA in the hypothalamus was studied following acute and chronic repeated stress. Delayed gastric emptying during acute stress (43.1 ± 7.8 %, n=6, P<0.05) was completely restored to normal levels (72.1 ± 2.4%, n=6) following chronic repeated stress. Impaired gastric motility induced by acute stress was also restored following chronic repeated stress. Intracerebroventricular (icv)-injection of oxytocin (0.1 and 0.5 µg) restored the impaired gastric emptying and motility induced by acute stress. The restored gastric emptying and motility following chronic repeated stress was antagonized by icv-injection of oxytocin antagonists. Oxytocin mRNA expression in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus was significantly increased following chronic repeated stress. In contrast, increased corticotropin releasing factor (CRF) mRNA expression in the SON and PVN in response to acute stress was significantly reduced following chronic repeated stress. Our study suggests the novel finding that the up-regulation of central oxytocin expression is involved in mediating the adaptation mechanism following chronic repeated stress in mice.