Objective To create a mouse model of colorectal polyps with Apc-Kras-Cre gene mutations using the tamoxifen induction method. Methods Mice with Apc-Kras-Cre mutations were divided into four groups and injected intraperitoneally with different concentrations and dosages of tamoxifen for different durations, with group 1 injected with low dosage tamoxifen (5 mg / kg) for 1 day, group 2 injected with low dosage tamoxifen (5 mg / kg) for 3 days, group 3 injected with high dosage tamoxifen (50 mg / kg) for 1 day, group 4 injected with high dosage tamoxifen (50 mg / kg) for 3 days.C57BL/ 6J mice were used as a healthy control group and survival and changes in body weight were observed. All mice were euthanized 4 weeks post-tamoxifen induction and the colon length and number and size of intestinal polyps were observed.Histological changes in the intestinal tissue and polyps were detected by hematoxylin and eosin staining. Results The survival rate of male mice was higher (P<0. 001) and the morbidity rate of male mice was lower compared with female mice (P<0. 05). The survival rate differed significantly among the four groups (P<0. 01). All groups showed significant changes in body weight compared with the healthy control group (P<0. 001). There were also significant differences in weight changes between tamoxifen-induced groups 1 and 2, between groups 2 and 3, and between groups 1 and 4 (P<0. 001, P<0. 01, P<0. 05, respectively). There were no significant differences in colon length between any treated group and the healthy control group (P>0. 05), but colon length did differ between tamoxifen-induced groups 1 and 3 ( P<0. 05). Polyp size varied in each group of tamoxifen-treated mice, with most polyps occuring at the distal end of the colon,while mice in groups 3 and 4 had more and larger polyps. Histopathological examination showed intestinal polyps with uneven and misaligned glandular and epithelial arrangements, a loosely-packed intestinal mucosal barrier, and irregularlydistributed crypts in tamoxifen-induced mice compared with the healthy control group, while mice in tamoxifen-induced groups 3 and 4 showed signs of inflammation and mice in group 4 showed necrosis of cells in some regions. Conclusions Tamoxifen-induced Apc-Kras-Cre model mice were successfully established, with the group 3 induction method being the most suitable.