Tissue inhibitor of metalloproteinase‐2 (TIMP‐2) and membrane‐type 1‐matrix metalloproteinase (MT1‐MMP) are always expressed during the cancer process. The aim was to identify which regions of the colon mucosa MT1‐MMP and TIMP‐2 begin to express themselves, as well as to establish their expression in relation to cell proliferation and mucin production. After intraperitoneal injection of 15 mg/kg of azoxymethane (AOM) at 4, 12, and 20 weeks, histological sections of the middle segment of the rat colon mucosa were evaluated by immunohistochemistry for cell proliferation and expression of MT1‐MMP and TIMP‐2 and histochemistry for mucin. As a result, a single dose of AOM initially increased the intensity of MT1‐MMP and TIMP‐2 expression in the conjunctive cells and glands, concurrently with alterations in the distribution of the mucin produced in the gland of the large intestine mucosa and cell proliferation. As a result, at 4 and 12 weeks, a single dose of AOM initially stimulated the expression of MT1‐MMP and TIMP‐2 in the conjunctive cells and glands with greater intensity. Changes in the cell proliferation and distribution of the mucin produced in the large intestine mucosa gland were observed. We conclude that MT1‐MMP and TIMP‐2 were first and strongly expressed in all cells of the colon glands, concurrently with an increase in cell proliferation and a diffuse dispersion of mucin, indicating the onset of the dysplasia process following a single dosage of AOM.