Objective To investigate the effects of 17α-estradiol (ESUB>2/SUB>α) on the release of β-amyloid protein (Aβ) with the transgenic cells β-amyloid precursor protein（APP）/ presenilin-1（PS1）Neuro-2a (NSUB>2/SUB>a), and explore the potential mechanism of such effect. Methods APP/PS1 NSUB>2/SUB>a cells were pretreated with 10×10SUP>-9/SUP> mol/L Eα for 2 days, then changed the culture medium, and treated with different methods: 1. Cells were treated with either E2α（25 nmol/L, 50 nmol/L, 100 nmol/L, 200 nmol/L）or vehicle, the protein level of Aβ and β-secretase-1（BACE1) both intracellular and extracellular of APP/PS1 N2a cells were detected by Western blotting. 2. Cells were treated with 100 nmol/L E2α, 20 nmol/L glucose and 5 IU glucose oxidase(GOX), followed by exposure to the glucose oxidase (G/Gox) to induce oxidative stress. After 24 hours, the change of the Reactive oxygen species（ROS）contents in APP/PS1 NSUB>2/SUB>a cells was observed for dihydroethidium(DHE). Results The extracellular level of Aβin APP/PS 1 NSUB>2/SUB>a cells treated with various concentration (25 nmol/L,50 nmol/L,100 nmol/L,200 nmol/L/L)ESUB>2/SUB>α were significantly decreased(EM>P/EM> <0.05). There was no change in the intracellular levels of Aβ and the levels of BACE1(EM>P/EM> >0.05). ESUB>2/SUB>α reduced the ROS produced by APP/PS1 NSUB>2/SUB>a cells after G/Gox treatment. Conclusion ESUB>2/SUB>α may reduce the production of extracellular Aβ and its mechanism may be related