Some phytochemicals demonstrate gastroprotective effects by inhibiting gastric acid secretion or through antioxidant action. One of these antioxidant phytochemicals which have been studied is gallic acid. However, its mechanism in the treatment and prevention of gastric ulcer remains unclear. This study evaluated the anti-ulcerogenic mechanism(s) of gallic acid (GA) and its novel synthetic derivative (GD). Adult male Sprague Dawley rats were orally pretreated with GA and GD and 30min later exposed to acute gastric ulcerogenesis induced by 95% ethanol (5ml/kg). Potential gastric chemoprevention of GA and GD were assessed using qualitative and quantitative evaluation of gastric lesions, gastric juice acidity, mucus production, histolopathology, PAS histochemistry, immunostaining of Hsp70 and Bax, nitric oxide, prostaglandin E2, TNF-α and thiobarbituric acid reactive substances (TBARS) assay. Oral administration of GA and GD (25 and 50mg/kg) inhibited significantly (P<0.05) ethanol-induced gastric lesions. Treatment with the compounds protected rat's stomach and modulated remarkably the levels of PAS-reactive substances, gastric pH, TBARS, immunological and apoptosis marker. The in vivo antioxidant properties, immunomodulator proteins and inhibition of mitochondrial apoptosis may contribute to the gastroprotective activity of gallic acid (GA) and its novel derivative (GD).