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Background: Osteoarthritis is a degenerative disease that is characterized by synovitis, subchondral bone remodeling, and chronicpainand progressive cartilage degradation. This studyaimsto investigate plasma estrogen receptor-a after intra-articular steroid injection in patients with TMJ osteoarthritis and evaluation of mandibular motion and pain intensity after injection. Methods: Twenty-seven Temporomandibular joint osteoarthritis (TMJ-OA) female patients: all of patients treated by intra-articular steroid injection to relive pain and prepared to further TMJ-OA treatment, only twenty-one followed up to further investigations and treatments plasma estrogen receptor-a level were estimated by Elisa method and mandibular (protrusive, lateral toward affected side, opening) movement measured and pain intensity also recorded by VAS scale before and after intra-articular steroidal injection. Results: Plasma estrogen receptors-a level was highly significant difference in patient complaining of TMJ-OA after intra-articular steroidal injection with p-value equal to 0.004. in this study patients with TMJ-OA was showed well improvement in mandibular range of motion at protrusive movement was highly significant difference p-value equal to 0.000, also lateral jaw excursiveand jaw opening movement, showed that improvement with highly significant difference p-value equal to 0.000. Regarding to pain intensity level VAS scale showed that highly significant difference p-value equal to 0.000 in reduction of pain intensity after intra-articular steroidal injection. Conclusions: In conclusion, one intra-articular TMJ steroidal injection reduced pain intensity by decreasing inflammatory response and also modulates ERalpha expression in the TMJ and passing to further TMJ-OA treatment.