Chronic hepatic injury is accompanied by a ductular response that is strongly correlated with disease severity and progression of fibrosis. To investigate whether anti-inflammatory drugs can modulate the ductular response, we treated mice suffering from a steatotic or cholestatic injury with anti-TNF-α antibodies (Infliximab) or glucocorticoids (Dexamethasone). We discovered that Dexamethasone and Infliximab can both modulate the adaptive remodeling of the biliary architecture that occurs upon liver injury and limit extracellular matrix deposition. Infliximab treatment, at least in these steatotic and cholestatic mouse models, is the safer approach since it does not increase liver injury, allows inflammation to take place but inhibits efficiently the ductular response and extracellular matrix deposition. Infliximab-based therapy could, thus, still be of importance in multiple chronic liver disorders that display a ductular response such as alcoholic liver disease or sclerosing cholangitis.