Beta-2-microglobulin (beta 2M) is associated with amyloidosis. The study of beta 2M kinetics can provide information on the elimination of this uremic toxin. A beta 2M kinetic model modified from Gotch, considering the volume changes between intracellular, interstitial, and intravascular compartments and the generation stimulation and inhibition during hemodialysis is proposed. The clinical experiments on 8 stable hemodialysis patients treated with polysulfone (F80) and polymethyl methacrylate (PMMA, BK2.1p) 3 times a week were conducted. There was an 18% decrease of beta 2M clearance in the period from 30 to 180 min with a time-averaged beta 2M clearance of 48 ml/min using polysulfone dialyzers (F80). In PMMA dialyzers, there was a 64% decrease of beta 2M clearance from 30 to 180 min with a time-averaged clearance of 56.3 ml/min. During hemodialysis, the generation rate was 0.379 mg/min in polysulfone and 0.828 mg/min in PMMA dialyzers. There was a stimulation generation of 0.309 mg/min in polysulfone and 0.749 mg/min in PMMA during hemodialysis. In conclusion, we provide a beta 2M kinetic model including volume changes, polymerization, generation stimulation, and inhibition that is similar to the human physiological condition. This model can be used for further clinical study.