Aiming to evaluate the protective effect of garlic on aspirin induced peptic ulcer in comparison with misoprostol and omeprazole drugs and its possible mechanisms. Forty white male albino rats were used. Total acid content, ulcer area/mm2, histological study, mucosal & serum Total Antioxidant Capacity (TAC) by calorimetry and mucosal & serum PGE2 and serum TNF-α by ELISA were assayed. Titrable acidity and total acid output decreased in garlic, misoprostol and omeprazole treated groups. Garlic, misoprostol and omeprazole improved gastric mucosa and decreased ulcer formation and ulcer area/mm2. Aspirin decreased PGE2 in gastric mucosa and serum. Co-administration of garlic to aspirin significantly increased PGE2 near to normal in gastric mucosa. Aspirin significantly increased serum TNF-α than control and other groups. Garlic is suggested to protect the stomach against ulcer formation induced by aspirin by reducing gastric acidity, ulcer area, improve gastric mucosa, increasing PGE2 and decreasing TNF-α.