Polyethylene glycol 400 (PEG 400) is widely used with a variety of pharmaceutical formulations, and is often added to dosing formulations in preclinical toxicity studies. The aim of the present study was to characterize the effects of PEG 400 on the rat gastrointestinal tract. Three dosage levels (5, 50 or 100 v/v%) of PEG 400 were administered at a volume of 5 ml/kg/day by gavage for 15 days to the rats (5 males and 5 females in each group). At the end of the treatment, the whole lengths of gastrointestinal tracts were examined pathologically. Although there were no gross abnormalities at necropsy, the histopathological examination revealed several changes localized to the stomach mucosa, but not in the intestine. The changes consisted of infiltration of eosinophils and globule leukocytes, increased in the height of the entire mucosal layer, elongation of the surface mucous epithelial and mucous neck cell layers with increased intracellular mucous in the glandular stomach, and the spongiosis (intercellular edema) of the squamous epithelium in the forestomach. These changes near the limiting ridge tended to increase in severity and extent in a dose-dependent manner. These results suggest that repeated oral administration of concentrated PEG 400 can easily induce the mucosal changes in the stomach of the rats.