Abstract: OBJECTIVE To investigate the effects of puerarin on β-amyloid precursor protein (APP) processing on SH-SY5Y cells transfected with human APP695 cDNAs and to explore the mechanism of puerarin on Alzheimer’s disease(AD). METHODS SH-SY5Y cells transfected with human APP695 cDNAs were cultured with 2.5, 5, 10 μmol·L^-1 puerarin，and cell survival was detected by MTT assay. The levels of Aβ_1-40 and Aβ_1-42 in conditioned were measured medium by using ELISA kit. The expressions of APP and b-secretase were detected by Western blot. The activity of secretase were measured by using a fluorescence spectrophotometer, the mRNA transcription of β-secretase were detected by RT-PCR. RESULTS Puerarin could dose-dependently reduce the levels of extracellular Aβ_1-40 or Aβ_1-42. After treatment with 2.5, 5 and 10 μmol·L^-1 puerarin for 24 h, the activity of β-secretase was decreased 15%, 30% and 40%, respectively(P<0.05). Compared with control group, puerarin 2.5, 5 and 10 μmol·L^-1 decreased β-secretase protein express to 82%, 71% and 45%, respectively(P<0.05). CONCLUSION Puerarin decreases Aβ levels by inhibit b-secretase expression and β-secretase activity, which may account for molecular mechanisms underlying the therapeutic efficacy of puerarin in AD patients.