The development of new therapeutic approaches against colorectal cancer requires preclinical studies in mice. In vivo imaging could greatly facilitate these trials, but the small size of the animals is a major limitation for the direct visualization of intestinal tissue. Here we report a method of in vivo imaging of the mouse intestine based on X-ray micro-computed tomography using multiple contrast agents. This method was validated in the model of non-cancerous polyp-like heteroplasia that spontaneously develops in the caecum area of Cdx2+/- mutant mice and in the model of colon adenocarcinoma induced by administration of the chemical carcinogen azoxymethane. As a simple and non-invasive method, multiple-contrast X-ray micro-computed tomography is appropriate for pre-clinical studies of intestinal diseases in living mice.