Introduction: The non-steroidal anti-inflammatory drug (NSAID) Piroxicam is widely used especially in treatment of osteoarthritis and rheumatoid arthritis. However, it has many side effects; the most common of them is gastrointesti nal intolerance and ulceration. The Nigella Sativa Oil (NSO) was reported to have anti-inflammatory and antioxidant properties. Aim of the Work: To investigate the histopathological effects of piroxicam on the gastric mucosa of adult male albino rats and the possible protective role of Nigella Sativa Oil (NSO). Materials and Methods: Fourty adult male albino rats were randomized into 4 groups (NN10). They received 2 ml of the following oral treatments through an orogastric tube: Group I (Control) received a single dose of saline, Group II (NSO) received a single dose of NSO; 10 ml/kg BW, Group III (Piroxicam) received piroxicam 20 mg/kg BW and Group IV (NSO/ piroxicam) received NSO one hour before administration of piroxicam. The gastric mucosa from the body of the stomach was processed for histological stains (H&E and PAS) and for examination with scanning electron microscope (SEM). Results: Piroxicam produced erosions, congestion, extravasated RBCs and inflammatory cell infiltration. It also led to increase in the gastric mucus. The SEM results revealed marked damage of the gastric mucosal surface and complete loss of the normal architecture. In NSO prior to piroxicam group, the structure of the mucosa was nearly similar to control by both light and SEM however, there was marked increase in mucus secretion. Conclusion: NSO can partly protect the gastric mucosa against piroxicam induced damage.