Objective To investigate the effect of high-flux hemodialysis on the serum beta 2-microglobulin(β2-MG) in long-term hemodialysis patients. Method Twenty-six long-term hemodialysis patients were selected, including 14 high-flux dialysis Group patients and 12 low-flux dialysis Group patients. The serum β2-MG levels were measured at the start and at the 2 weeks, 6 months of this study. The symptoms of joint pain were evaluated. Results The serum β2-MG levels decreased significantly after high-flux dialysis. The percent reduction of β2-MG levels was 45.2% by the first high-flux dialysis. At start and 2 weeks, 6 months of this study, The serum β2-MG levels in high-flux dialysis patients were 66.3 mg/L, 51.2 mg/L and 47.6 mg/L, respectively. The symptoms of joint pain significantly improve of in high-flux dialysis patients. During the 6 months of low-flux dialysis,the plasma β2-MG levels(66.8 mg/L and 65.5 mg/L at the beginning and at the end of low-flux dialysis) and symptoms of joint pain unchanged. Conclusion Our study demonstrated that symptoms of joint pain are improved significantly with high-flux dialysis which is an effective treatment to decrease the serum β2-MG levels in long-term hemodialysis patients. Membrane flux is the main determinant of β2-MG levels in long-term hemodialysis.