The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic saline (10 ml kg(-1)) and the ethanol group had taken 1 ml (per rat) absolute alcohol by gavage. The third and fourth groups also received NS (500 mg kg(-1)) and TQ (10 mg kg(-1)) by gavage 1 h before alcohol administration, respectively. Both drugs (NS and TQ) could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index values. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells (MC) and gastric erosions in ethanol treated rats. The NS treatment significantly decreased the number of MC and reduced the area of gastric erosions. Likewise, TQ treatment was also able to reduce the number of MC and the gravity of gastric mucosal lesions, but to lesser extent compared to NS. Gastric tissue histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats, and NS or TQ treatment reversed these increases. Results obtained from this study suggest that both drugs, particularly NS could partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects could be due to their antiperoxidative, antioxidant and antihistaminic effects.