Tissue inhibitors of metalloproteinase (TIMP) are important participants in various physiological processes that involve tissues remodeling. They help maintain a delicate balance between physiological degradation and synthesis of the extracellular matrix. A better understanding of TIMP activity will be helpful in understanding the etiology of periapical lesions and their means of treatment. The fibroblast is a prominent cellular component of the periapical tissues. The potential implications of cytokine-mediated tissue destruction still remain to be elucidated. The purpose of this study was to determine the effects of interleukin (IL)-1α and transforming growth factor (TGF)-β on the expressing of TIMP-1 by primary gingival fibroblast cultures. After exposure to cytokines for 8 h, total RNA in gingival fibroblasts was isolated and evaluated by reverse-transcriptase polymerase chain reaction. Densitometric analysis of the TIMP-1 mRNA gene expression, after normalization by β-actin, demonstrated that exposure to IL-1α resulted in a decreased level of TIMP-1 mRNA compared with the control groups. However, the TIMP-1 mRNA was up-regulated by TGF-β. In addition, when the cells were cultured in combination with TGF-β (1 ng/ml) and IL-1α for 8 h, the level of TIMP-1 mRNA was dramatically reduced. These results demonstrated that in human periapical tissue cytokines differentially and specifically regulate expression of TIMP-1 mRNA. An understanding of the actions of cytokines on gingival fibroblasts may result in new therapies to augment current treatment of periapical lesions.