Abstract: Aim: Preliminary study revealed that gedunin and photogedunin, from Xylocarpus granatum exhibit anti-ulcer property. In an attempt to clarify the mechanism involved in its anti-ulcerogenic potential, an advanced studies to examine their effects on potent gastric acid secretagogues i.e., plasma gastrin and gastric mucosal histamine in pyloric ligation induced ulcer model. In addition, an evaluation of the cytoprotective function of these compounds by assessing the gastric PGE2 levels in alcohol induced gastric ulcer model. Methods: Adult Sprague Dawley rats, weighing 180-220 g procured from National Laboratory Animal Centre, CDRI, were used in the study. Rats were housed three to four per cage, in a room with temperature regulated at 22±2°C, with a 12 h/12 h light/dark cycle (lights on 07:00 h, lights off 19:00 h). Standard chow pellets and water were given ad libitum, except during the period when food deprivation was applied. Compounds of Xylocarpus granatum and standard drugs like omeprazole (10 mg kg-1) and sucralfate (500 mg kg-1) were prepared in 1% carboxymethyl cellulose (CMC) as suspension and administered orally 45 min prior to exposure of ulcerogens to the animals at a volume of 1 mL/200 g of body weight. All animals were deprived of food for 16 h before ulcerogens exposure and were divided into three groups, (n = 6). Control group of animals were treated with vehicle 1% CMC. Compound gedunin and photogedunin (20 mg kg-1, p.o.) were tested against alcohol and pyloric ligation induced gastric ulcer model. Standard anti-ulcer drugs, omeprazole (10 mg kg-1, p.o.) were treated in pyloric ligation model and sucralfate (500 mg kg-1, p.o.) in alcohol induced ulcer model. Results: Gedunin and photogedunin exerted significant acid lowering activity in pyloric ligated rats as evident through reduced free acidity and total acidity as well as in vitro H+K+-ATPase activity. Also, both compounds normalized the plasma gastrin and tissue histamine level compared to ulcerated rats. Contrastingly, both compounds illustrated no significant increase in gastric PGE2 level and mucin content compared to ulcer control rats. Conclusion: Thus, the study suggested that gedunin and photogedunin imparts gastro-protection through antisecretory mechanism.