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Aims: β-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and β-catenin in type 2 diabetes mellitus (DM) patients remains unclear. Methods: Colorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1 year (n = 27) and non-DM patients without hyperglycemia (n = 20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n = 6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/β-catenin signaling was assessed immunohistochemically and phosphorylation of β-catenin was assessed by immunofluorescence. Results: Compared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/β-catenin signaling were significantly higher in the DM group(all p < 0.01). The proliferative index correlated positively with β-catenin expression (Spearman correlation coefficient = 0.55; p < 0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of β-catenin were detected in the DM group (all p < 0.01). Conclusions: Enhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. β-Catenin accumulation with altered phosphorylation correlated with the proliferative changes. [ABSTRACT FROM AUTHOR]