The purpose of this study was to assess the therapeutic effect of positron emission tomography agent [¹⁸F]-labeled 2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG) in a colorectal cancer mouse model. Three (3) tumor-bearing mice groups were treated with different doses of ¹⁸F-FDG. Mice were imaged by positron emission tomography with ¹⁸F-FDG before and after treatment weekly and the tumor growth rate was calculated. Tumor, brain, heart, and kidney of mice were analyzed for expression of glucose transporters and vascular endothelial growth factor (VEGF) by immunofluorescent staining, and the presence of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. All 3 treated groups showed significant ¹⁸F-FDG reduction compared with the control group (p < 0.05). With higher treatment dose, better treatment response was observed. The tumor growth rate of all 3 treated groups was also significantly decreased after treatment (p < 0.05). Immunohistochemistry showed that tumors expressed more glucose transporters than in brain, heart, and kidney. The ¹⁸F-FDG treatment of mice resulted in apoptotic cell death in all 3 treated groups, which showed significant higher apoptotic cells than the control group (p < 0.05). The study suggests that ¹⁸F-FDG has a therapeutic effect in colonic cancer animal model, which indicates the potential for the development of positron therapy for colonic cancer and other cancers.