We examined the feasibility of the human immunodeficiency virus (HIV) vector-mediated local expression of angiostatin in the treatment of murine collagen-induced arthritis in a mouse model generated by immunization with bovine type II collagen and Freund's complete adjuvant. The HIV vector containing the murine angiostatin expression unit (HIV-angiostatin) was injected into right knee joints after arthritis development; the HIV vector containing the enhanced green fluorescein protein (EGFP) marker gene (HIV-EGFP) was injected into the left joints. Quantitative histological evaluation demonstrated that synovial cell hyperplasia and pannus formation were significantly reduced in the right knee joints as determined by this protocol. Suppression of radiographical changes in the ipsilateral paws was also observed. These results indicate that the HIV vector-mediated expression of angiostatin efficiently inhibits the progression of collagen-induced arthritis. Angiostatic gene therapy may provide a new approach to the effective treatment of rheumatoid arthritis.