Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterise signalling via these hormones in the brain, liver and adipose tissue, however, very little is known of their emerging role in peripheral signalling particularly in epithelial tissues. This study profiles insulin, leptin and adipokine receptors in the rat colon, revealing novel microanatomical location of these receptors and thereby supporting a potential role in regulating colonic tissue. Potential involvement of insulin, leptin and adiponectin receptors in increased risk of colon cancer was investigated using Sprague-Dawley rats either resistant or susceptible to diet-induced obesity. Regulation of insulin, leptin and adiponectin receptors as a consequence of differing levels of adiposity was assessed regionally in the colon with regard to plasma levels of insulin, leptin and adiponectin, and in response to treatment with the chemical carcinogen, 1,2-dimethylhydrazine. However, significantly increased fat mass, increased levels of plasma insulin, leptin and triglycerides, previously associated with an increased risk of colon cancer, were not associated with promotion of precancerous lesions in the experimental rats or deregulation of insulin, leptin or adiponectin receptors. These findings do not support a direct link between the deregulation of insulin and adipokine levels observed in obese rats and an increased risk of colon carcinogenesis.