The endothelin family has been related with several pathological diseases including cardiovascular disorders, hypertension and cancer. However, little is known about endothelin system in early stages of colorectal cancer and there are no studies evaluating differences in proximal and distal colon segments. To deepen in this issue, we have studied the endothelin's family gene and protein expression in normal mice and early stage of a mice model of Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS) induced colorectal cancer in proximal and distal segments. Additionally, using nonlinear microscopy (NLM) techniques, we have characterized collagen changes in early stages of cancer disease development. In the present study, we have found significant differential gene expression and protein localization between these colon regions, which allow us to hypothesize a new role for the ET-2 as an early marker of colon cancer development.