Aims: To determine the effect of low-intensity pulsed ultrasound (LIPUS) on cyclooxygenase-2 (COX-2) expression and related mechanisms by using cultured articular chondrocytes derived from porcine mandibular condyles after treatment with interleukin-1 beta (IL-1β). Methods: Chondrocytes were derived from porcine mandibular condylar cartilage and cultured. The cells were treated with or without 10 ng/mL IL-1β. At the same time, the cells were exposed to LIPUS for 20 minutes. After LIPUS exposure, the conditioned medium was changed to a fresh one without IL-1β, and the cells were incubated for 0 to 24 hours. The effects of LIPUS on IL-1β-treated chondrocytes were examined in terms of the expression of p-integrin β1, COX-2, and phosphorylated extracellular signal-related kinase (p-ERK) 1/2 by real-time polymerase chain reaction (PCR) and Western blot analyses. Differences in the means among multiple groups were examined by oneway analysis of variance (ANOVA) for all groups at each time point, followed by a Scheffé multiple comparison test as a post-hoc test; Student t test was also used. Results: COX-2 mRNA level was upregulated by the treatment with IL-1β and was suppressed significantly (P .01) by LIPUS exposure. Furthermore, LIPUS enhanced gene expression and phosphorylation of integrin β, and it inhibited the expression of p-ERK 1/2. Conclusion: LIPUS exposure inhibited IL-1β-induced COX-2 expression through the integrin β1 receptor followed by the phosphorylation of ERK 1/2. Despite the restricted duration of its effect, LIPUS is suggested to be a potential candidate as a preventive and auxiliary treatment to suppress the degradation of articular chondrocytes in temporomandibular joint osteoarthritis. Keywords: cyclooxygenase-2 (COX-2), low-intensity pulsed ultrasound (LIPUS), mandibular condylar cartilage, mechanical stress, osteoarthritis (OA)