Background: It has been shown that Achillea wilhelmsii, a plant used in traditional medicine to treat gastrointestinal disorders, has the antibacterial, antioxidant and antispasmodic effects. However, the effects of Achillea wilhelmsii on gastric acid secretion have not been detected yet. Materials and Methods: Twenty four male Wistar rats (200-250 g) were randomly divided into two groups (case and control). After anesthesia by sodium thiopental (50 mg/kg, ip) tracheostomy, laparatomy and gastrodeodenostomy were performed for each rat. Gastric secretions were collected through a tube inserted in the stomach and extended toward duodenum. Using the maceration method, different doses of the extract (0.5, 1, 2 mg/kg) were prepared in a volume of 1 ml. The same amount of normal saline was used in control group. Two samples of the gastric secretion were collected by 15 minute intervals. The total titrable acid was measured by a titrator. The data were analyzed using unpaired t-test and the results were reported with a significance level of 0.05. Results: The extract significantly inhibited the basal acid secretion in a dose-dependent manner. A concentration of 2 mg/kg of the extract showed a stimulatory effect on acid secretion. Vagotomy prevented the inhibitory effect of extract on gastric acid secretion. There was no difference between the effects of extract on control and stimulated vague group. Conclusion: The results indicated the inhibitory effect of extract on basal acid secretion. The comparison of extract effect on basal acid secretion at basal and vagotomized conditions showed that the inhibitory effect of the extract was mediated by the inhibition of gastric vagal activity. The extract could not inhibit the stimulated gastric acid secretion