Rheumatoid arthritis (RA) displays a chronic inflammatory joint disease, accompanied by symmetric polyarthritis (PA) which evokes synovial inflammation, cartilage damage, and bone erosion. Patients with RA are routinely treated by immunosuppressive drugs. The therapy of inflammatory diseases and degenerative disorders with Low-dose radiotherapy (LD-RT) (single doses from 0.3 to 1.0 Gy) represents a low cost therapy with low toxicity, and is able to substitute at least in part treatment with drugs. The efficiency of LD-RT has already been proven in several animal models of inducible arthritis. In the present study we used a human TNF transgenic mouse model to examine the effects of LD-RT on PA. We observed a significant temporal improvement of the clinical progression of disease when mice were irradiated at the beginning of the disease. These data emphasize the role of LD-RT in clinical settings to treat patients with chronic and degenerative disorders and diseases.