Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer (CAC). Methods A colitis-cancer model in C57BL/6 mice was established using azoxymethane (AOM) combined with dextran sulfate sodium (DSS). Samples were collected at 7，10，and 14 weeks post-modeling to observe spleen index，colon length，weight，and colon mass per unit length. Histopathological changes in the mouse colon were observed using hematoxylin and eosin (HE) staining and Masson staining. Real-time fluorescent quantitative PCR was used to detect the expression of cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b，Lrp5，Axin2，and Znrf3 at different pathological stages. Multiple immunofluorescence histochemistry (mIHC) and immunofluorescence (IF) were employed to detect the expression of cancer-associated fibroblasts (FAP)，CD44，proliferation marker Ki67，and goblet cell MUC2 protein. Additionally，colon organoids were isolated and cultured in vitro from model mice at 10 and 14 weeks to observe changes in organoid morphology and marker expression. Results At 7 weeks，AOM/DSS-induced mice showed reduced，distorted，and branched crypt structures of colon with a small amount of collagen fibers. At 10 and 14 weeks，model mice exhibited varying degrees of intraepithelial neoplasia in colon，with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining. Compared with the normal group，the mRNA levels of CD44 and Wnt2b were significantly increased (p<0.05) and Axin2 was decreased (p<0.01) in the colon of model mice at 14 weeks. Compared with the 7-week mice，the levels of Wnt2b，Lrp5，and Znrf3 were increased (p<0.01，p<0.05，p<0.01)，and Axin2 was decreased (p<0.01). mIHC staining showed increased expression of FAP and CD44 in the colon of model mice at 10 and 14 weeks，with decreased MUC2 expression. The colon organoids showed cystic dilation，especially those from the 14-week model，with more prominent expression of Ki67 and CD44. Conclusion The AOM/DSS-induced mouse model exhibited chronic colonic inflammation，low-grade intraepithelial neoplasia，and high-grade intraepithelial neoplasia at 7，10，and 14 weeks，respectively. The pathological microenviroment were characterized by fibroblast activation and abnormal proliferation of epithelial cells.