The ECM is a complex fibrillar network of macromolecules that provides structural and mechanical support to the intestinal tissue. One abundant component of the ECM observed in the Salmonella-driven intestinal edema is the mechanosensitive glycoprotein fibronectin. Combining mechanosensitive staining for relaxed fibronectin with total fibronectin revealed that fibronectin fibers present in the edema are in a tensed molecular conformation. Co-staining with fibrin(ogen) indicates a provisional matrix, similar to what is observed in response to skin injury. The absence of low tensional fibronectin fibers and the additional finding of a high number of protease inhibitors in the edema proteome could indicate a critical role of stretched fibronectin fibers in maintaining tissue integrity in the severely inflamed cecum. Understanding these processes may provide valuable functional diagnostic markers of intestinal disease progression.