Osteoarthritis (OA) is a chronic degenerative joint disease and a leading cause of disability. It involves articular cartilage destruction and a whole joint inflammation. In spite of OA pathogenesis is still unclear, new studies on the OA pathophysiological aetiology and immunomodulation therapy continuously achieve significant advances with new concepts. Here, we focus on the indoleamine-2,3-dioxygenase1 (IDO1) activity in the osteoarthritis (OA), which is one of the noticeable enzymes in the synovial fluid of arthritis patients. It was recognized as an essential mediator of autoreactive B and T cell responses in rheumatoid arthritis (RA) and an interesting therapeutic target against RA. However, the role IDO1 plays in the OA pathogenesis hasn't been discussed. The new OA experimental analysis evidenced IDO1 overexpression in the synovial fluid of OA patients, and recent studies reported that IDO1 metabolites were found higher in the OA synovial fluid than RA and spondyloarthropathies (SpA) patients. Moreover, the positive relation of IDO1 metabolites with OA pain and joint stiffness has been confirmed. Thus, the IDO1 plays a pivotal role in the pathogenesis of OA. In this review, the role IDO1 plays in the OA pathogenesis has been deeply discussed. It could be a promising target in the immunotherapy of OA disease.