The physiological integrity of the gastric mucosa is dependent on the balance between the mucosal protective and aggressive factors. Medicinal plants or their derivatives generally exhibit gastroprotective effect by promoting the protective factors against the aggressive factors of the gastric mucosa. The study was conducted to elucidate the gastroprotective mechanism of the methanol extract of C. owariensis (MECo) in rats. Twenty male Wistar rats were divided into four groups, which include control groups A and B – given distilled water – and treated groups C and D – animals given 100 and 300 mg/kg MECo respectively for 28 days. After the treatment period, gastric mucosal injury was induced for groups B-D by pyloric ligation method. The gastric tissue of animals was collected, processed for histology (haematoxylin and eosin technique), histochemistry (periodic acid-schiff technique) and immunohistochemical staining (for Bcl-2 & Bax proteins). The results of the gastric histomorphology showed prominent and widespread mucosal erosion in positive control group B compared to normal control group A, while treated groups C and D showed only mild or focal mucosal erosion. Furthermore, the histochemical results showed significant increase in mucous cell population in treated groups C and D compared to positive control group B. The immunostaining results showed significant up-regulation of anti-apoptotic Bcl-2 protein and down-regulation of pro-apoptotic Bax protein in the treated groups C and D compared to the control groups A and B. In conclusion, the findings of this study indicate that the increased mucous cell population and modulation of apoptotic signaling highlights the mechanism of gastroprotective activity of MECo.