Periodontitis is an inflammatory disease of the supporting tissues of the teeth. Interleukin (IL)-13 is a multifunctional T-helper type2 (Th2) cytokine that can diminish inflammatory responses. I investigated using ELISA the effects of IL-13 on transforming growth factor-beta (TGF-) and matrix metalloproteinase-1 (MMP-1). MMP-1 was detected using immunohistochemistry. Gingival fibroblasts were stimulated with IL-13 or together with tumor necrosis factor- (TNF-). I found that macrophage-like cells, fibroblast-like cells, vascular endothelial cells and gingival epithelial cells were stained more intensely for MMP-1 and were observed more frequently in the periodontitis affected group than in the control group. The cultured gingival fibroblasts with IL-13 produced more TGF- than unstimulated cells. After stimulation with additional TNF-, MMP-1 production was diminished. IL-13 may play a role in regulating collagen homeostasis in gingival fibroblasts. IL-13 induces both up-regulation of TGF-, a cytokine known to stimulate production of collagen, and down-regulation of collagen-destroying MMP-1 production. This effect may be strong during periodontitis when Th2 cells assist T cells.