Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that leads to joint destruction and disability. Despite a significant progress in administration of biological agents for RA patients, there is still a need for improved therapy. Intravenous-immunoglobulins (IVIG) , a pooled polyspecific immunoglobulin-G (IgG) extracted from 20,000 healthy subjects, showed beneficial therapeutic effect in patients with immune-deficiency, sepsis, and autoimmune diseases. The current study aim to investigate the beneficial effect of treatment with IVIG in established collagen induced arthritis in DBA/1j mice. Murine arthritis was induced in DBA/1j mice. The treatment with IVIG started when the disease was established. The clinical score was followed twice a week until day 48. The mice were bled for plasma, the paws were H&E stained. Cytokine profile in the plasma was analyzed by Luminex technology, titers of circulating anti-collagen antibodies in the plasma was tested by ELISA. Our results show that treatment with IVIG in murine, significantly rreduced the clinical arthritis score (P<0.001). Moreover, mode of action show that IVIG significantly reduced circulating level of inflammatory cytokines (IFN, IL-1β, IL-17, IL-6, TNFα) (P<0.001), inhibit anti-collagen antibodies (P < 0.001) in the plasma of CIA mice. Importantly, histopathological examination revealed that IVIG treatment prevented the migration of inflammatory immune cells into the cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Our results proved for the first time the valuable anti-inflammatory treatment of IVIG in experimental RA. We propose IVIG therapy for a subgroup of patients with as rheumatological-related diseases.