The purpose of this investigation was to investigate the roles that tumour necrosis factor-alpha (TNF-alpha) and apoptosis play during acute inflammation of the temporomandibular joint (TMJ). Adult male Sprague-Dawley rats were injected with complete Freund's adjuvant (CFA) into the TMJ or kept as uninjected controls. The TMJ tissues were removed 2 days post-injection to mimic conditions of acute inflammation and analysed for changes in expression of TNF-alpha, the receptor TNF-R1, caspase-3 and -8, and apoptosis. Concentrations of TNF-alpha, TNF-R1, caspase-3 and -8, and apoptosis were significantly elevated in CFA-injected animals compared to uninjected controls. Tissue incubation with TNF-alpha caused a significant increase in caspase-3 and -8. Also, levels of apoptosis were significantly increased during inflammation, which could be inhibited by the addition of either anti-TNF-alpha neutralising antibody or caspase inhibitors. TNF-alpha may play a significant role in the onset of acute CFA-induced TMJ inflammation, and activation of apoptosis signalling pathways may be involved.