The aim of this study is to elucidate the effects and the mechanism of rebamipide, omeprazole, and their combination treatment on quality of peptic ulcer healing (QOUH). Peptic ulcer models were induced by acetic acid exposure of the serosa of rat stomach. Forty Sprague-Dawley (SD) rats were divided randomly into four groups of ten rats each. Saline 2 ml/d (group 1), rebamipide 60 mg/kg/d (group 2), omeprazole 10 mg/kg/d (group 3) as well as its combination regimen (group 4) were administrated for 7 days. After sacrifice, size of the ulcer and focal layer structures were measured in vitro by miniature ultrasonic probe, and the mucosal sections were stained with hematoxylin and eosin (HE) for histological examination; the levels of interleukin (IL)-8/prostaglandin E(2) (PGE(2)) were evaluated by enzyme-linked immunosorbent assay (ELISA) and malondialdehyde (MDA) level was evaluated by thiobarbituric acid (TBA) method. Macroscopically, compared with the control group, the maximal diameters of the ulcers in the medication groups were significantly reduced (P < 0.05), and the layer echo structures of gastric wall were partially rebuilt. Histologically, ulcer range and inflammatory infiltration were less severe compared with the control group. In addition, mucosal MDA and IL-8 levels were significantly decreased, while PGE(2) level was significantly increased in the medication groups. Between the two monotherapy groups, there was no statistical difference in terms of PGE(2) and MDA levels. However, PGE(2) level was significantly increased, while MDA and IL-8 levels were significantly decreased in the combination group. Rebamipide as well as omeprazole and the combination regimen may improve QOUH through increasing the level of PGE(2), decreasing the levels of IL-8 and MDA in gastric mucosa, and this may potentially result in reduced recurrence of ulcer; moreover, the combination regimen was identified as having more antiulcer effects than monotherapy.