Background: Angiotensin converting enzyme (ACE) upregulation in stromal cells of joints affected by rheumatoid arthritis may lead to higher tissue angiotensin II that is a vasoconstrictor and mitogen factor. To date, the role of angiotensin II on regulating blood flow in inflamed joints has not been studied. Methods: Acute and chronic joint inflammation was induced in rabbits by intra-articular injection of carrageenan and antigen-induced arthritis method, respectively. The ACE level of synovial fluid and the response of joint blood flow to angiotensin II, angiotensin II receptor antagonist, and the role of nitric oxide (NO) in modulation of the effects of angiotensin II on joint blood vessels were examined. Results: The synovial fluid level of ACE was significantly increased during the process of inflammation and angiotensin II increased joint vascular resistance dose-dependently in both acute and chronically inflamed joints. The angiotensin 1 receptor antagonist losartan completely blocked the vasoconstrictor effect of angiotensin II on joint blood vessels and induced vasodilatation. Nitric oxide synthase inhibitor N-omega -nitro L- arginine methyl ester (L-NAME) increased joint vascular resistance and augmented vascular response of inflamed joints to angiotensin II. Conclusion: Angiotensin II receptors in joint blood vessels are angiotensin -1 subtype, and inflammation significantly increases the activity of synovial fluid ACE. Nitric oxide plays a significant role on regulating joint blood flow and in modulation of angiotensin 1 receptor-mediated vasoconstriction of inflamed joint blood vessels.