Background and Objectives: The cause and pathophysiology of rheumatoid arthritis has not been fully understood and an experimental model of this disease is essential for research on the problem. In this research study, establishment and histopathological changes of chronic arthritis due to intra-articular antigen injection was used as a model of experimental rheumatoid arthritis. Materials and Methods: Thirty three New-Zeeland white rabbits were sensitized by subcutaneous injection of combination of methylated bovine serum albumin (MBSA) and Freund’s complete adjuvant (FCA) at days 1 and 14. Sensitized animals at day 28 received intra-articular injections of MBSA. At days 7, 14, 21, and 28 post-injection, excised knee joints were investigated for routine light microscopic changes. Results: It was found out that at day 7 there are fibrinous exudates in the joint space and pericapsular soft tissue, edematous synovial villi, and an intact cartilaginous site of joint. At day 14, lymphoid follicle formation at pericapsular area, short and widening of synovial villi, superficial erosion of joint cartilage (perichondritis) was observed. Thereafter, at day 21 increased secondary lymphoid follicles with active germinal centers at pericapsular areas, papillary hyperplasia of the synovial villi, thinning of the cartilaginous site of joint with mononuclear cellular infiltrates (chondritis) was noted. In addition, day 28 was demarcated by continuation of the chondritis and beginning of osteitis, granulation tissue formation (Pannus) at cartilaginous site of joint, and fibrotic changes of the synovial villi. Rare findings including pseudocyst space and palisading ranuloma at the pericapsular area was also observed. Conclusion: Antigen-induced chronic arthritis in the knee joint of the rabbit is a good experimental model to evaluate the pathogenesis and/or effects of drug interferences in the rheumatoid arthritis.