Objective To study the mechanism of gastric bypass operation on treatment of type 2 diabetes mellitus, recognize the etiology and pathogenesy of the disease and frame therapy strategy for type 2 diabetes mellitus. Methods The literatures about gastric bypass operation on treatment of type 2 diabetes mellitus, including clinical cases reports and evidence-based studies were reviewed. Results Gastrointestinal bypass operation was regarded as an effective treatment for type 2 diabetes mellitus. There were three hypotheses of therapy mechanism: early delivery of nutrients to the distal intestine, exclusion of the proximal intestine and incretin/anti-incretin. Conclusion Gastrointestinal bypass operation is now considering as an effective treatment, there is still a lack of basic experimental studies to clarify the mechanism.