Collagen-Induced Arthritis (CIA) is a complex model of autoimmune-mediated arthritis that is regulated by multiple genetic and environmental factors. CIA is induced in rats by immunization with native type II collagen and develops joint pathology similar to that of rheumatoid arthritis. This chapter details methods for the extraction and purification of native type II collagen from sternal and articular cartilage, an arthritis induction protocol that has resulted in reproducible CIA expression in several rat strains from year to year and criteria for measuring clinical, radiographic and immunological outcome parameters characteristic of CIA.