Peptic ulcer owes its pathological features to disregulated oxido-nitrosative and necrotic changes in gastrointestinal mucosa. Xanthium strumarium L. is a ubiquitous, abundant herb possessing an array of pharmacological properties. In view of anti-inflammatory and antioxidant activity of Xanthium strumarium L., the present investigation was designed to unravel its antiulcer potential in pylorus ligation induced gastric ulcer in laboratory animals. X. srtumarium L. leaves were extracted by refluxing with 95 % ethanol to obtained X. srtumarium L. ethanolic extract (XSEE). After 1 h pretreatment period of XSEE (100, 200 and 400 mg/kg) gastric ulcer was induced by ligation of pylorus portion of stomach. Various parameters including volume of gastric fluid, pH of gastric fluid, free as well as total acidity were measured in the gastric fluid whereas ulcer area, ulcer index, mucin content, superoxide dismutase, myeloperoxidase, nitric oxide, total calcium, histamine level, membrane bound inorganic phosphate (Na-K-ATPase), TNF-${alpha}$ level, DNA fragmentation were determined in the gastric tissue. Pretreatment with XSEE (200 and 400 mg/kg) significantly and dose dependently (P<0.01 and P<0.001) decreased ulcer area, ulcer index, macroscopical gastric damage score, volume of gastric fluid, free acidity as well as total acidity and mucin content. It also significantly increased pH of gastric fluid. Rats treated with XSEE (200 and 400 mg/kg) significantly and dose dependently (P<0.01 and P<0.001) attenuated decreased level of superoxide dismutase, nitric oxide and Na-K-ATPase. It also significantly decreased level of myeloperoxidase, calcium and inflammatory cytokine i.e. TNF-${alpha}$. XSEE treated rats showed significant reduction in the pylorus ligation induced apoptotic changes. The possible mechanism by which Xanthium strumarium exerts its gastro-protective action may be due to free radical quenching, DNA repair and down regulation of oxidative-nitrosative stress along with cytokines.