Previous studies show that octreotide LAR causes regression of gastric ECL-cell carcinoids, reducing both number and size of tumours. This study examines the molecular mechanisms behind the antiproliferative effect of octreotide on the oxyntic mucosa. Female rats received octreotide LAR for 21 days. Serum gastrin was measured and tissue samples for RNA extraction and histology collected from the oxyntic mucosa. Affymetrix analysis showed regulated genes related to apoptosis and proliferation, and a large group of regulated growth-related transcription factors. Verification by real time qRT-PCR showed a high degree of consistency to the microarray results. Supporting the molecular results, histomorphometry showed significant decreases in the number of gastric glands, cells per gland and length of glands, and a tendency towards increased apoptosis and decreased proliferation. Thus, octreotide exerts a negative effect on oxyntic mucosal growth, and induces extensive gene expression changes relevant to growth regulation.