Objective: Our study aimed to detect whether 450 nm blue laser can be applied effectively and safely in endosocopic submucosal dissection (ESD) system for surgery in colonic tissue. Background data: Semiconductor blue laser has been applied in surgery due to its excellent cutting property, however, whether blue laser can be applied in colonic surgery has not been reported. Materials and methods: Porcine colon tissues were vaporized by 450 nm blue semiconductor laser at 10-25 W and at working distances from 0.5 to 3 mm, with a three-dimensional scanning system. Moreover, we designed an ESD model and applied blue laser at 10 W on porcine colonic tissues with this system. Dimensions of the vaporized tissues and coagulation zones were assessed under microscopy. Results: Since the thickness of colonic wall is no more than 1 mm, first we determined the cutting property and safety of blue laser on porcine colon tissue and found that blue laser at 10 W made lesions shallower than 1 mm and the depth of vaporization can be controlled effectively within muscularis mucosa and submucosa. Moreover, a large scale of porcine colonic tissue was vaporized precisely by blue laser at power of 10 W with the ESD system ex vivo. Conclusions: Our results indicate that 450 nm blue laser at 10 W can be well controlled for laser-tissue interaction with excellent cutting efficiency and less thermal damage in adjacent tissues especially side of the submucosa. Therefore, 450 nm semiconductor blue laser could be a safe alternative approach for colonic surgery.