Recently, we developed that the mice chronic vicarious social defeat stress (cVSDS) model, known as validated animal model of depression, showed the irritable bowel syndrome (IBS)-like symptoms such as chronic intestinal motility changes and abdominal hyperalgesia without organic lesions. Previously, we reported that a selective delta opioid receptor (DOP) agonist KNT-127 improved the depression-like behaviors observed in mice cVSDS model. In the present study, we examined the effects of KNT-127 on the IBS-like symptoms in cVSDS model. The model mice were prepared by exposure to repeated psychological stress for 10 days in C57BL/6J mice. KNT-127 was administered subcutaneously (s.c.) and microinjected into the Insular cortex (IC) 30min before the test, respectively. KNT-127 (10mg/kg, s.c.) significantly improved increased intestinal transit ratio in the charcoal meal test and hypersensitivity symptoms in the capsaicin-induced hyperalgesia test, respectively. In addition, KNT-127 (300ng/mouse) in IC was normalized their intestinal transit ratio. These results suggested that KNT-127 improved the IBS-like symptoms in cVSDS mice via DOPs in IC. We proposed that DOP agonist have the potential to be an effective treatment for IBS, capable of breaking the vicious cycle in gut-brain interactions.