Objective To investigate the therapeutic effect of far infrared radiation in the treatment of chronic lymphedema of extremities and to explore the mechanism. Methods Thirty-two patients with chronic lymphedema of extremities in stage Ⅱ and Ⅲ were treated with far infrared radiation. Before and after the treatment, clinical effects related to extremities swelling were evaluated, including the amount of fluid, the measurement of limb circumference, the thickness of dermis and subcutaneous tissue, the quality of life and the adverse reactions. Eleven patients(34%) went through laboratory index evaluation including cytokines and macromolecules associated with the swelling(IL-6, leptin, hyaluronan and total protein) in serum and tissue fluid of the lymphedema extremities. Results After treatment, the clinical evaluation showed the decrease of extracellular fluid(0.763±0.259) Kg(P<0.001), the decrease of fluid in the extremities(1.204±0.737) Kg(P <0.001), the decrease of circumference of extremities(2.0 ±1.3) cm(P <0.001), the decrease of thickness of skin and subcutaneous tissue(0.07±0.10) cm(P<0.001);(0.32±0.35) cm(P<0.001), and the improvement of quality of life(1.375±0.942)(P<0.001). And the laboratory index evaluation found that the concentration of IL-6 in serum was increased(13.947±4.436) pg/mL(P <0.05), the level of leptin in tissue fluid was decreased(11456.210 ±12656.400) pg/mL(P <0.01), and the ExtraM-Hyaluronan and ExtraM-total protein in affected extremity were both decreased(0.267±0.171) g(P<0.01);(0.137±0.083) Kg(P <0.01). Conclusion Far infrared radiation treatment can effectively reduce the water, lipid, protein and hyaluronan deposited in the swollen tissues and improve limb swelling symptoms by increasing the concentration of IL-6 in the body and reducing the level of leptin in the limbs.