Glucagon-like peptide-2 (GLP-2) is able to induce gastric fundus relaxation with implications for emptying rate or feeling of satiety. GLP-2 actions are mediated by GLP-2 receptor (GLP-2R), located on enteric neurons and myofibroblasts in mouse gastrointestinal tract. It is unknown if changes in the GLP-2R levels occur in different nutritional states, so we examined the GLP-2R expression in gastric fundus and analyzed the gastric mechanical responses to GLP-2 in mice fasted or fed high-fat diet. The gastric mechanical activity was recorded in vitro as changes of intraluminal pressure and GLP-2R expression was examined using reverse-transcription real-time polymerase chain reaction and western blotting. GLP-2R expression in fundic region from 12-h or 24-h fasted mice was reduced in comparison with standard diet (STD)-fed mice and returned to control values after re-feeding, while GLP-2R expression was increased in HFD-fed mice. The GLP-2 efficacy in inducing gastric relaxation, normalized to isoproterenol response, was decreased in stomach from fasted mice and it was increased in stomach of HFD-fed mice compared to STD-fed mice. In conclusion, the nutritional state influences GLP-2R expression in mouse stomach. The changes in the GLP-2R expression are associated to modifications of GLP-2 gastric relaxant efficacy. The GLP-2 action could represent an adaptive response to the fast or to the increased nutrient intake.