Background and Objective: Circadian rhythm hormones melatonin (MEL) and 5-Methoxytryptophol (5-MTX) have antioxidant and anti-inflammatory effects on the biological systems. The aim of this study was the investigation of Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), Rapid Accelerated Fibrosarcoma-1 (Raf-1) and Signal Transducer and Activator of Transcription 3 (STAT3) inflammatory markers in the temporomandibular joint arthritis (TMJA) model) and effects of pineal hormons melatonin (MEL) and 5-Methoxytryptophol (5-MTX) on these parametres. Materials and Methods: Wistar albino (200-250 g) 40 rats of both sexes were used in this study. The arthritis model was created by intraarticularly injecting zymosan dissolved in physiological saline solution (2 mg/40 mu L) into the left TMJ'S, while the sham group was created by only injecting 40 mu L physiological saline solution. Intraperitoneal applications of MEL (15 min before zymosan) and 5-MTX (30 min before zymosan) were conducted for therapy. Data were analyzed using one-way analysis of variance (ANOVA). Results: The animals were decapitated after 6 h. COX-1, COX-2, Raf-1 and STAT-3 levels were examined with the RT-PCR technique. Articular structural damage was assessed histologically. In arthritis group, the activity of COX-2, Raf-1 and STAT3 were increased, therapy applications led to decreased these parameters. However, a significant difference was not observed in COX-1. In the histological evaluation, obvious articular degeneration and disc congestion in the arthritis group regressed with therapy. Conclusion: In this study, COX-2, Raf-1 and STAT3 have been suppressed by the therapeutic effect of MEL and 5-MTX.