Prolactin (PRL) is a polypeptide hormone produced by specialized cellsin the anterior pituitary gland and in several sites outside the pituitary. Inaddition to its physiological actions which include various roles inreproduction and lactation, prolactin has been demonstrated to exert numberof homeostatic biological activities that may affect the immune functions.Interestingly, PRL is now identified as a common mediator of animmune-neuroendocrine network. Elevated serum PRL concentrations oftencorrelate with abnormalities in immune responses. Our present study aimed tofurther explore the possible potential role of PRL in the pathogenesis ofinduced rheumatoid arthritis.An experimental model of Rheumatoid arthritis (RA) was induced by asingle dose of bovine collagen type II emulsified in complete Freund'sadjuvant and injected at the base of each rat's tail. Study groups included: acontrol group represented vehicle-treated rats and a main experimental groupin which autoimmune rheumatoid arthritis was induced (collagen inducedarthritis (CIA)). All animals were left for a period of 30 days which was thetime needed for the pathogenesis of the disease and drug treatment.The experimental animals in the second group were randomlysubdivided into the following: a) an untreated group of CIA rats, b) CIA ratsin which hyperprolactinemia was induced by administration ofmetoclopramide, c) CIA rats in which hypoprolactinemia was induced byadministration of bromocriptine, d) CIA rats treated with prednisone and finally e) CIA rats treated with a combination of bromocriptine andprednisone.Results of the present study revealed that the enhanced serum PRL levelsestimated in the CIA rats were associated with a significant increase in thelevels of TNF-α and exacerbation of the inflammation in the knee joints,especially after induction of hyperprolactinemia together with increased PRLRgene expression which was significantly down-regulated inhypoprolactinemic- and prednisone-treated groups.Thus, we conclude that, there is a strong positive correlation which linksplasma prolactin levels and the arthritic index.