This study aims to observe the curative effect of modified Wuqi decoction (MWQD) on non-steroidal anti-inflammatory drugs-induced gastric ulcer (NSAIDU) and explore the mechanism. 80 NSAIDU subjects were enrolled into the study according to inclusion criteria and divided into the treatment group (CM, n=40) and the control group (CON, n=40) using double-blindly randomized method. The patients in the CM group were administered with Pantoprazole Sodium Enteric-coated Capsules together with MWQD, while the patients in CON group were administered with Pantoprazole Sodium Enteric-coated Capsules and control granules. The treatment lasted for 2 months. All subjects went through Carbon 13 urea breath test to detect Helicobacter Pylori (Hp), and the following procedures were conducted before and after the treatment: (a) the executors of this study blindly filled in the scale assessment of positive symptoms of subjects; (b) 3 ml venous blood was collected for the PGE2 and IL-1 test via ELISA and the expression of TNF-α; (c) the subjects were examined via gastroscopy to observe the gross morphology of gastric mucosa, then the gastric mucosa was received HE staining after pathologic biopsy; and moreover, the COX2 expressions of all the gastric mucosa specimens before and after treatment were tested via immunohistochemistry. The subjects with positive Hp were treated with radical treatment in combination with this therapy protocol. Before treatment, the inflammatory factor, endoscopic grades and gastric biopsy assessment have no significant difference (Ρ>0.05) between CM and CON groups, i.e., they exhibit the comparability. After treatment, the overall effective rates of CM and CON groups are 100% and 90%, respectively; immunohistochemical results illustrate that COX2 protein expression of CM group is higher than that of CON group (Ρ<0.05), while IL-1 and TNF-α expressions are lower than those of CON group (Ρ<0.05); PGE2 expression increases (Ρ<0.05). MWQD is proved to be effective in relieving inflammatory reactions by inhibiting inflammatory factors such as IL-1 and TNF-α, upregulating the expression of PGE2/COX2 to strengthen the protective and self-healing functions of gastric mucosa, thereby enhancing the clinical cure rate and lowering the recurrence rate of NDGU. This study can provide a therapy protocol for long-term Aspirin-applied NSAIDs.