Testosterone, the predominant androgenic hormone, has a wide range of biological actions. It has been found to exert its androgenic and anabolic effects on both reproductive and non-reproductive target tissues. Since, it is now generally recognized that androgens can be involved in several pathological disorders in particular inflammatory or auto-immune diseases, thus, the present study aimed to further explore the possible potential role of testosterone in modulating the immune response in rheumatoid arthritis induced in castrated rats. This was achieved experimentally by induction of collagen induced arthritis (CIA). An intradermal injection of a single dose of collagen type ІІ emulsified in complete Freund׳s adjuvant was supplied at the base of each rat's tail. Study groups included: 1) Control group which represented vehicle-treated normal rats, 2) Sham operated group in which CIA was induced, 3) The main experimental group including castrated rats which, were randomly subdivided into the following: a) Control group of normal castrated rats, b) Castrated-untreated CIA rats, c) ) Castrated-CIA rats treated with testosterone, d) ) Castrated-CIA rats treated with testosterone co-supplemented with a non-steroidal aromatase inhibitor "letrazole”. All animals were left for a period of 30 days (which was the time needed for the pathogenesis of the disease and drug treatment). Results of the present study revealed that castration resulted in the development of a pro-inflammatory state with a marked exacerbation in the sequence of the disease as regards significant elevation of the serum levels of the inflammatory biomarkers associated with deterioration of the histopathological features upon applying castration prior to arthritic induction. Upon supplying the castrated-CIA rats all through the period of arthritic induction with testosterone replacement therapy, a condition which is less aggressive with significant decrease in the serum inflammatory biomarkers levels has been observed. Moreover, a marked significant improvement was observed upon supplying the castrated-CIA rats with an aromatase inhibitor (letrazole) combining testosterone replacement therapy. Thus, we conclude that the present findings as regards the protective role of testosterone and its effects in modulating immune response are consistent with observations which were collected previously as regards the potential benefits of testosterone replacement therapy.