Collagen-induced arthritis (CIA) in mice is an animal model for rheumatoid arthritis (RA) and can be induced in DBA/1 and C57BL/6 mice using different protocols. The CIA model can be used to unravel mechanisms involved in the development of arthritis and is frequently used to study the effect of new therapeutics. The development of a CIA model in C57BL/6 mice recently enabled researchers to use knockout mice on this background for arthritis research.In this chapter, the protocol for induction of arthritis in both mice strains is described, including the monitoring of clinical arthritis and paw swelling in the mice during the experiment. Furthermore, protocols for decalcification of paws and for the detection of collagen-specific antibodies in mice sera are described.