We recently demonstrated that endothelin-1 (ET-1) was strongly expressed in inflamed gingival tissues, but the biological role of ET-1 in gingival tissue remains unknown. This study focused on the relationship between ET-1 and interleukin-1β (IL-1β), an important cytokine during the periodontal inflammatory process. We determined the protein levels of ET-1 and IL-1β in gingival tissues from patients and examined whether ET-1 could regulate the expression of the IL-1β gene and protein in oral epithelial cells and fibroblasts in vitro. There was a significant correlation between the levels of ET-1 and IL-1β in 26 gingival tissues, as determined by ELISA. Following the confirmation of two specific ET-1 receptors (ET_A and ET_B receptors) on the cultured cells, the effects of ET-1 stimulation on IL-1β mRNA and protein expression were evaluated by RT-PCR and ELISA, respectively. The IL-1β mRNA and protein levels were enhanced by ET-1 stimulation in a dose-dependent manner, and the enhancement of IL-1β was inhibited by ET_A or ET_B receptor antagonists. These findings indicate that ET-1 is involved in the regulation of IL-1β expression in gingival tissues and suggest that ET-1 signaling to the cells may be a therapeutic target for treating IL-1β-dependent inflammatory responses.