The objective of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis in an indomethacin-induced SD rat model. Rats were randomly divided into six groups: G1 (normal group), G2 (control group, indomethacin-induced gastritis), G3 (positive group, indomethacin-induced gastritis and ranitidine 50 mg/kg), G4 (LJF-HE-L group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 30 mg/kg), G5 (LJF-HE-M group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 60 mg/kg), G6 (LJF-HE-H group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 120 mg/kg). In the group treated with LJF-HE (G4, G5, and G6), gastric mucosal damage, gastric juice secretion and pepsin activity were significantly decreased compared to the control group. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r), histamine receptor H2 (H2r) and H+/K+ ATPase in the gastric lesions. The plasma levels of TNF-α and IL-1β significantly decreased in LJF-HE (G4, G5, and G6) treated groups compared with control. The plasma level of PGE2 was also significantly increased by LJF-HE (G5 and G6). These results suggest that LJF-HE (G4, G5, and G6) has the ability to inhibit on indomethacin-induced gastritis.