The aim of this study was to determine the localization of tenascin-C, fibronectin and collagen types III and IV during regeneration of the rat submandibular gland. After 7 days' obstruction, the regenerating glands were collected at days 0, 1, 3, 5, 7, 11 and 14 after duct release to study regeneration. Immunohistochemical staining revealed that tenascin-C was strongly expressed in the epithelial cells of duct-acinar structures at days 0-3, and down-regulated in its expression from day 5 to 11, though weak expression was detected in the intercalated duct and acinar cells of the normal gland. Strong labeling of fibronectin was detected around duct-acinar structures during days 0-3 of regeneration. Type IV collagen was expressed strongly in the thickened basement membrane of acinar cells and duct-acinar structures during days 0-3, but weakly around large ducts, though type III collagen was expressed at consistent levels. These findings suggest that tenascin-C and fibronectin affect only the duct-acinar structures, and type IV but not type III collagen is involved in the regeneration of acinar cells.