Tube feedings and intragastric glucose prevent stress ulceration by unknown mechanisms. We tested the hypothesis that glucose protects the gastric mucosa by direct repletion of glycogen stores. We compared the effects of enteral glucose with enteral lipids in the rat restraint model. The rats were given equal volumes of 0.9% saline, 20% lipids, or 25% glucose during a 4-h period of restraint stress. The effects of each treatment on gastric residual volume and luminal pH, as well as on stress lesion formation were measured. Both enteral nutrients significantly reduced the number of mucosal lesions compared to saline. In conjunction with their protective effect, both nutrients significantly increased both gastric residual volume and luminal pH. As stress-induced prolonged gastric contractions are related to mucosal injury in this model, the nutrient solutions may have been protective in part because they increased gastric volume and prevented mechanical trauma to the mucosa. We conclude that tube feedings do not prevent stress ulceration by glucose's repletion of local glycogen stores, as lipids and glucose were equally effective. Both increased intragastric volume and increased intraluminal pH associated with administration of enteral nutrients may contribute to their protection of the gastric mucosa from stress ulceration.