To understand the effects of γ-ray irradiation (IR) on the proliferation of gastric mucosal cells and to investigate the possible mechanisms that affect gastric mucosal cell proliferation.C57BL/6J mice were exposed to IR at various doses (4, 8, and 15 Gy). We measured the changes of gastric mucosal BrdU-positive cells and the expression of β-catenin protein in the isthmus of fundic glands at days 1, 3, and 5 after irradiation.Our data showed that the mice that received 15 Gy IR died within 4 days. IR caused gastric mucosal injury in mice, and the degree of injury increased along with the increasing doses. Compared with the control group, the proliferation of gastric mucosal cells was inhibited 1 day after irradiation. Cell proliferation was recovered on day 5 after low-dose (4 and 8 Gy) IR, while proliferation was continuously inhibited after high-dose (15 Gy) IR. β-catenin expression was increased and had a translocation in the isthmus of gastric mucosa.These findings suggest that gastric mucosa is sensitive to irradiation. The Wnt/β-catenin pathway is activated and plays a role in cell proliferation of gastric mucosa upon irradiation.