Chronic inflammation is recognized as a cancer-promoting factor. The full range of inflammatory processes is still under definition. Local changes of immune activation can induce fast collagen remodeling in the tissue. Reciprocally, collagen accumulation can affect the local immunity. We have shown that immunological activation of a tissue (by bacteria or chemicals) quickly modifies the colon mucosa structure. Using a rat model of chronic colitis (dextran sodium sulphate – DSS – induced colitis) and of carcinogenesis (azoxymethane – AOM - carcinogen for the colon) we have shown that, in both models, inflammation produce remodeling of the collagen scaffold, even when the mucosa appears recovered at the distance of 1 month from the acute induction. This occur dispite apparently normal o reduced levels of local cytokines as a smoldering inflammation. Immunological data and confocal microscopy suggest that normally the microbiota can elicit homeostatic regulation in the healthy rat colon mucosa. The modulation can be due to an “inflammatory threshold” establishing the range of tolerance toward the pro-inflammatory activation. The smoldering inflammation has dis-balance between pro-inflammatory and regulatory signals and, dispite low cytokine levels overcomes the inflammatory threshold. Underhand, smoldering inflammation is capable to continue to damaging the tissue structure and leading to either chronic inflammatory diseases or cancer development.