The aim of this study was to investigate the effect various mediators in synovial fluid (SF) on the pathogenesis of temporomandibular disorders (TMD) and to evaluate the relationship between clinical and radiological features of temporomandibular joint (TMJ) diseases. Patients who had received SF sample during arthrocentesis because of TMD were included in this study. Clinical and radiological records were evaluated retrospectively. Enzyme-Linked ImmunoSorbent Assay (ELISA) method was used for analysis of aggrecan, adiponectin, resistin, apelin, Vascular Endothelial Growth Factor (VEGF) and Prostaglandin E2 (PGE2) in SFs. 59 joints of 41 patients were included in the study. Anterior disc displacement with reduction (ADDwR) was detected in 22 joints, anterior disc displacement without reduction (ADDwoR) was detected in 29 joints and osteoarthritis (OA) in 8. In OA group, PGE2 level was significantly higher than the other groups (p = 0.029). Aggrecan and PGE2 levels were statistically higher in joints with localized pain (p = 0.030, p = 0.029). The aggrecan level was statistically significant higher in patients who had degenerative changes in radiological examinations (p = 0.044). Resistin was correlated with PGE2 and aggrecan (p = 0.011), and apelin showed positive correlation with VEGF (p˂0.001). The detection of aggrecan and adipokines in SF may be a precursor of degenerative joint disease and it should be taken into account that the presence of localized pain in the joint area may be an early sign of degenerative changes. Copyright © 2021. Published by Elsevier Ltd.