Matrix metalloproteinase-1 (MMP-1) plays an important role in the degradation of collagen in inflammatory diseases. The aim of this study was to investigate the cellular expression of MMP-1 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in gingival fibroblasts co-cultured with monocytes and the possible mediating role of intercellular adhesion molecule-1 (ICAM-1). In co-cultures, the expression of MMP-1 and TIMP-1 increased in fibroblasts, but not in monocytes, although the number of MMP-1+ and TIMP-1+ adhered monocytes increased. Moreover, ICAM-1 expression in both fibroblasts and adhered monocytes increased. In the presence of an anti-ICAM-1 antibody, the expression of MMP-1 in fibroblasts decreased whereas the number of TIMP-1+ adhered monocytes increased. The p38 MAPK inhibitor SB203580 reduced MMP-1 expression in fibroblasts, as well as ICAM-1 expression in both fibroblasts and adhered monocytes. The results suggest that co-culture with monocytes enhances cellular expression of MMP-1 and TIMP-1 in gingival fibroblasts, and that the increased MMP-1 expression, in contrast to TIMP-1, is partly mediated by the adhesion molecule ICAM-1 and the p38 MAPK signal pathway.