Objective: To investigate the effects of hypoxia on the expression and activity of SIRT1 and its regulatory mechanisms on human immune function. Methods: Human primary peripheral blood monocytes(HPBMs) were cultured in vitro under normal oxygen and hypoxia(1% O2) conditions. The protein expression of SIRT1 was detected by Western blot. Real-time PCR was performed to examine the mRNA levels of SIRT1,NAMPT and HLA-DR-琢. Activity assay kits were used to detect the activity of SIRT1 and value of NAD+/NADH. Results: SIRT1 protein level was inhibited with peak inhibition occurring at 12 h post exposure to hypoxia. The mRNA levels of SIRT1 and NAMPT in cells cultured in hypoxia were significantly lower than that cultured in normal oxygen(P < 0.05). In addition,the enzyme activity of SIRT1 and the value of NAD+/NADH were also significantly decreased (P < 0.05). Resveratrol, which is the agonist of SIRT1,rescued the decreased expression of HLA-DR-琢 induced by hypoxia. Conclusion: The CⅡTA-dependent HLA-DR-琢 expression was decreased,and accompanied with a decrease in the expression and enzyme activity of SIRT1 in macrophages exposed to hypoxia. These results revealed that SIRT1 may play a critical role in regulating adaptive immunity.