Omeprazole, a proton pump inhibitor (PPI), is widely used in treatment of peptic ulcer, gastro esophageal reflux disease and eradication of Helicobacter pylori. PPIs inhibit final gastric acid secretion stage by blocking H+/K+-ATPase. But the mechanism except for gastric antisecretory effect has not understood clearly. So, we examined the effects of omeprazole on the levels of gastrointestinal peptides (somatostatin, motilin, gastrin, vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP)) in plasma from healthy subjects. After a single oral administration of omeprazole, the plasma omeprazole concentration was highest at 120 min. Omeprazole caused a significant increase of plasma somatostatin-immunoreactive substance (IS) levels at 60-240 min and plasma motilin-IS levels at 120-180 min, compared with a placebo group, respectively. The physiological release of plasma gastrin-IS was reduced by the administration of omeprazole at 60 min, but the medicine did not alter the levels of VIP-, CGRP- and SP-IS. These results suggested that the pharmacological effects of omeprazole on regulation of gastrointestinal function are closely related to changes of somatostatin-, motilin- and gastrin-IS levels in human plasma.