Although obesity is a risk factor for colorectal cancer, the underlying mechanism is not clear. Adiponectin is an adipokine that binds to 2 types of receptors, AdipoR1 and AdipoR2. The plasma concentrations of adiponectin are reduced in obese individuals and adiponectin has been reported to have anticarcinogenic properties. Furthermore, AdipoR1 and AdipoR2 have been reported to be expressed in several malignancies. However, little is known about the expression of AdipoR1 and AdipoR2 in colorectal cancer and its clinicopathological implications. In addition, the relationship between adiponectin and colorectal cancer has not yet been determined. Here, we sought to investigate adiponectin and adiponectin receptors in relation to colorectal cancer. AdipoR1 and AdipoR2 immunostaining was detected in 72 and 68% of human colorectal cancer tissue, respectively. AdipoR1 and AdipoR2 expression levels were inversely related to T stage. The lowest AdipoR1 and AdipoR2 expression were detected in poorly differentiated adenocarcinoma. RT-PCR also showed the expression of AdipoR1 and AdipoR2 in HCT116 and SW620. MTT assay and TUNEL assay demonstrated the tendency of growth inhibition and apoptosis induction in both cell lines after full-length adiponectin treatment although statistically insignificant. Microarray analysis revealed several gene responses to full-length adiponectin, including upregulation of ENDOGL1 and MT1G. In conclusion, AdipoR1 and AdipoR2 may be intimately related to the progression of colorectal cancer. Further studies may be warranted to assess adiponectin and its receptors as a novel target for inhibition of colorectal cancer growth.