Objective: The present studies were aimed at evaluating whether an aqueous extract of Tulsi leaves is capable of ameliorating piroxicam-induced gastric injury in rats. Methods: Male Wister rats were used for the present studies. The aqueous Tulsi leaf extract (TLE) [25, 50, 100 and 200 mg/kg bw] was administered orally to the fasted rats (water ad libitum), one hour prior to the piroxicam treatment. Results: The aqueous leaf extract of Tulsi was found to protect the gastric mucosa from becoming ulcerated following piroxicam treatment, in a dose-dependent manner. Pre-treatment of rats with increasing doses of TLE protected the rise in the level of lipid peroxidation, reduced glutathione from being decreased as well as protected the activities of the antioxidant enzymes indicating it may have protected the gastric tissue from piroxicam-induced injury. The results of the biochemical analyses were supported by macroscopic and microscopic studies of gastric tissue. Conclusion: From the results it may be concluded that aqueous leaf extract of Tulsi may be a safe gastro-protective agent and may find extensive pharmaceutical applications especially in situations where the use of NSAIDs is the only choice.