The mechanisms devoted to the protection of the extracellular matrix collagen from the inflammatory insult are not fully understood. We investigated the presence of the immunosuppressive glycoprotein alpha1-microglobulin in healed tissues such as scars and periprosthetic membranes, comparing them with normal skin. Immunohistochemistry showed that alpha1-microglobulin was mainly present along collagen fibrils and in the epidermis. The presence of this protein was confirmed by Western blot of the tissue homogenates, while ELISA showed lower levels in the healed tissues. In vitro, the purified alpha1-microglobulin bound collagen by a cooperative mechanism and attenuated the collagen-induced activation of the mononuclear cells.