Matrix metalloproteases (MMPs) are proteolytic enzymes involved in tissue remodelling and extracellular matrix (ECM) turnover. They are secreted in a latent form and activated at the cellular surface by a membrane type-1 MMP (MT1-MMP) and a tissue inhibitor of MMP-2 (TIMP-2) that is also responsible for striking a balance between the proteolytic enzymes and TIMP-2. In allergic contact dermatitis (ACD) patients, MMP-2 and MMP-9, two members of the MMPs family, were increased during the challenge phase, in involved but not uninvolved skin. In contrast, TIMP-2 was more evident in uninvolved than involved skin, while no differences were observed with regard to MT1-MMP staining. Comparing the serum of ACD patients with that of healthy subjects, these differences were not observed. These data suggest that MMP-2 and MMP-9 could play a role in the mechanisms inducing alterations of the epidermal architecture, and in the pathogenesis of the lesions.