Purpose: Recent epidemiological studies have consistently demonstrated a significant link between obesity and increased incidence of malignancy including colon cancer. However, the significance of adiponectin and leptin, a peptide hormone secreted by adipocytes, in colorectal carcinogenesis has not been clearly established. In this study, we aimed to comprehensively examine changes in the expression levels of adiponectin, adiponectin receptors, and leptin in normal-adenoma-carcinoma sequence of the colon. Methods: We enrolled 78 subjects (10 healthy controls, 29 patients with colorectal adenoma and 39 patients with colorectal cancer (CRC)) who underwent polypectomy of colorectal adenoma or surgical resection of primary colorectal cancer. The serum adiponectin and leptin concentrations were measured by ELISA. The mRNA expression levels of two AdipoRs, AdipoR1 and AdipoR2, in each tissue were examined by quantitative real-time polymerase change reaction (qRT-PCR). The protein expression patterns of adiponectin, AdipoRs, and leptin were comparatively analyzed by immunohistochemical staining. Results: The serum adiponectin concentration was lower in patients with colorectal adenoma and CRC than healthy controls in male group. However, no difference of serum adiponectin concentration between patients with adenoma and CRC was observed. The serum leptin concentration showed no significant difference between each tissue groups. The mRNA expression levels of AdipoRs were significantly decreased in colorectal adenoma and CRC tissues than in normal colon tissues. However, there was no difference in the mRNA expression levels of AdipoRs between colorectal adenoma and CRC. In immunohistochemical staining, adiponectin was expressed in the subepithelial thin layer of spindle-shaped cells in normal colon tissues, not in the epithelium. The expression pattern of adiponectin in colorectal adenoma and CRC showed that its expression of the thin layer was obliterated, while the expression was increased in the mesenchyme. The expression of AdipoRs, which is positive in the normal epithelial cells in immunohistochemical staining, showed weak to negative intensity in cancer epithelium. There was no significant difference in the expression pattern of leptin among the groups. Conclusion: These results suggest that adiponectin in serum and colon tissue changes reciprocally to each other in the sequence of normal-adenoma-carcinoma. Serum adiponectin and AdipoRs expression is probably related to the early step of colorectal carcinogenesis. Additionally, it is possible that signal pathway between adiponectin in mesenchyme and AdipoRs in epithelium takes a role in early step of colorectal carcinogenesis.