Rodrigues et al. demonstrated that the DMH-induced colorectal cancer model in rats is a valid tool to investigate the association of ACF with colorectal cancer. ACF may be regarded as early morphological markers in the pathogenesis of welldifferentiated tumors in colon carcinogenesis. The results of this study indicated that the number of ACF and the number of foci containing different number of crypts in the STZ+DMH group increased compared with the DMH group. In the DMH group, 89.4% ACF had one or two crypts, and only 10.6% ACF had three or more crypts. However, in the STZ+DMH group, the incidence of ACF with one or two crypts was 67.7% and 32.3% had three or more crypts. In contrast, the STZ group had no ACF formation. Epidemiologic findings have shown that the incidence of colorectal cancer in diabetic patients was closely related to the diabetes duration. Thus, we inferred that a much longer time is needed for the rats in the STZ group to develop ACF. The significant increase of foci containing $3 crypts and the detection of tumor-like tissue in the STZ+DMH group indicated that the presence of diabetes mellitus shortened the duration of tumorigenesis. In accordance, Zaafar et al. have reported that diabetes promotes the size of cell and the inflammatory reactions in the mucosal layer like lymphoid proliferation, congestion of blood vessels and fibrosis. At the end of our present study, tumors were found both in the DMH group and STZ+DMH group. The incidence, number and size of tumors in the STZ+DMH group increased compared with that of DMH group. In contrast, no tumors were found in the STZ group. Whereas, no lesions in general were visualized by gross examination in Zaafar’s study. Different animals were selected in the experiments may be the possible explanation for this phenomenon. Mice were used in their experiment while rats were selected in our study. The gap of body size may reflect the size of the tumor, so tumors were difficult to be visualized in mice colon tissues. However, there was no significant difference in the incidence of tumors between the STZ+ DMH group and DMH group in current result. Possible explanations for this phenomenon may include the limited sample size, with only 15 rats in each group. Overall, these data demonstrated that diabetic rats have a high risk of colorectal cancer. Rapid proliferation is the main feature of tumor cells. Proliferating cell nuclear antigen is a DNA clamp that acts as a processivity factor for DNA polymerase d in eukaryotic cells and is essential for replication. Bostick et al. have reported that the expression of PCNA is closely related to the proliferation of cell in colon tissue and can be used as a very reliable indicator to evaluate the proliferation dynamics of tumor cell. The present study demonstrated that PCNA was highly expressed in all tumor tissues and that the expression of PCNA was increased in colonic ACF compared with that of normal intestinal glands. PCNA expression can reflect cellular proliferation activity and is used as a reliable index for evaluating the kinetics of tumor cell proliferation. Our results showed that PCNA was expressed in DMH-induced colon cancer cells, and the strongest proliferation activity was observed in the DMH+STZ group. These data indicated that STZ treatment could promote DMH-induced cell proliferation. Previous hypothesis about the possible mechanisms involved in DM-related cancer was the abnormal increase of insulin-like growth factor-1 and Fingolimod 162359-56-0 vascular endothelial growth factor in the serum that can lead to the occurrence of tumors by promoting the transformation and proliferation of colorectal.