Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease traditionally believed to be driven primarily by the adaptive immune cells. However, a large infiltrate of innate cells can be seen in the inflamed joints of patients. Furthermore, macrophages and the complement system, important parts of the innate immune system, have been implicated to have a role in chronic RA. To investigate the role of the innate immune system in RA a new model, independent of the adaptive immunity was created; called mannan-induced collagen antibody induced arthritis (mCAIA) in which the role of macrophages and complement system was confirmed as enough to drive a chronic arthritis in a reactive oxygen species (ROS) deficient milieu. ROS has previously been implicated to affect the development of arthritis. To further investigate this a transgenic ROS inducible mouse was created to investigate the role of ROS at different stages of the disease; this mouse is deficient of ROS until induced. ROS was shown important for regulating both the primary and the effector phase of the disease, thus postulating a broad role for ROS as regulators of autoimmune disease. Interestingly, the collagen specific T cells were of importance primarily in the beginning of disease but no difference could be seen between sick and healthy mice in later disease, while the macrophages seemed of importance throughout the disease. Another regulator of the autoimmune disease was found to be the macrophage mannose receptor (MR). Loss of MR caused both higher severity in mCAIA and in the psoriatic arthritis model mannan-induced psoriasis (MIP). In conclusion, a hypothesis is presented where the adaptive immunity (e.g. T cells and autoantibodies) is of importance primarily in the initiation of arthritis, but the chronic arthritis is primarily driven by the innate immunity (e.g. macrophages, complement cascade and neutrophils). Further studies are required to confirm this, but if true it could affect the manner we treat RA patients or a subgroup of them, focusing it more towards medicine targeting the innate immunity.