This study aimed to use immunohistochemical analysis of the expression of tumor necrosis factor-alpha (TNF-alpha) in the temporomandibular joints (TMJs) of patients with anterior disc displacement without reduction (ADD-woR) and rabbits to examine the effects of TNF-alpha on the development of degenerative changes in ADD. Six temporomandibular discs from 5 patients with articular disc perforations caused by ADDwoR were examined using immunohistochemistry. Tissues distant to the perforated area served as controls. The histological changes were observed, and elevated expression levels of TNF-alpha were detected. To investigate the changes in the mandibular condyle, rabbits were used in animal experiments because the mandibular condyles of patients with ADD cannot be resected. The discs of the TMJs were surgically displaced anteriorly in 20 adult rabbits. Five additional rabbits served as non-surgical controls. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery, and the histological changes were observed. The TNF-alpha expression levels in the cartilage were detected by immunohistochemistry. The expression of TNF-alpha in the cytoplasm of the chondrocytes of normal condyles exhibited sporadic scattering in the hypertrophic zone. Two and four weeks after ADD, the TNF-alpha-positive cells were aligned in the hypertrophic zone and located near the proliferating zone and the center of the hypertrophic zone. Then, after eight and twelve weeks, brown staining was observed in both the cytoplasm and nucleus of chondrocytes in the outer hypertrophic zone. The expression of TNF-alpha in the cartilage of the condyle after ADD was different relative to the normal cartilage and was altered during the ADD period. TNF-alpha may be related to the process of cartilage degeneration during ADD.