The aim of this study is the investigation of synoviocytes, cytokines and metalloproteinases in the synovial inflammation model which is created by zymosan application to temporomandibular joint (TMJ) and effects of pineal hormones melatonin (MEL) and 5-methoxytryptophol (5-MTX) on these parameters. 200-250 g Wistar albino rats of both sexes were used for modeling arthritis in this study. Arthritis model was created by intraarticularly (i.a.) injecting 2 mg zymosan in 40 ml saline into the left temporamandibular joint of the rats while the sham group was created by only injecting 40 ml saline solution (intraarticulary). MEL and 5-MTX administration was made intraperitoneal before zymosan injection. 6 hours after zymosan or saline administration of MEL and 5-MTX the synovial fluid was collected from the animals and the synovial membrane was collected for histological assessment. The administration of zymosan increased the release of IL-1 beta and TNF alpha and the activity of metalloproteinases (MMM-9) and metalloproteinases-2 (MMP-2) and with this administration values got closer to the sham group. The histological evaluation showed significant increase in the intensity of synoviocytes that arose in the inflammation was found to subside. In conclusion, MEL and 5-MTX reducing inflammation in arthritis suggests these agents might constitute a new therapeutic principle clinically.