The precise mechanisms of acute damage and the role of gastric mucosal blood flow in gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remain uncertain. The aim of this study was to evaluate the preventive effect of rebamipide on gastric mucosal injury and reduction of gastric mucosal blood flow (GMBF) after ibuprofen administration. Twenty healthy volunteers were randomized two groups. The rebamipide group took ibuprofen, 1800 mg/day, and rebamipide, 100 mg t.i.d., for 7 days. The placebo group took ibuprofen, 1800 mg/day. The numbers of gastric ulcer subjects were three in the placebo group and zero in the rebamipide group. The mean modified Lanza score after ibuprofen administration was significantly higher in the placebo group than the rebamipide group (2.9+/-1.7 vs. 1.3+/-1.0, respectively; P=0.032). The GMBF of the placebo group was significantly decreased at antrum from baseline, from 2.8+/-0.5 to 2.0+/-0.5 tissue perfusion units (P=0.005). There was no difference in GMBF change in the rebamipide group. Gastric mucosal injury was correlated with GMBF reduction in antrum (r=-0.677, P=0.001). In conclusion, it is suggested that the decrease in GMBF may have been associated with NSAID-induced gastric mucosal injury, and rebamipide may have prevented NSIAD-induced gastric mucosal injury by maintaining GMBF in healthy subjects.