Objective · To investigate the effect of microenvironment on the of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in PC12 cells. Methods · The PC12 cells were respectively treated with thapsigargin (Tg), lipopolysaccharide (LPS), H2O2, hypoxia incubator and hypoglycemic medium to produce mild endoplasmic reticulum stress (ERS), inflammatory environment, mild oxidative stress, hypoxia and low glucose conditions. Western blotting and fluorescence quantitative PCR were used to detect the of BACE1 protein and BACE1 mRNA. Results · After PC12 cells were treated with Tg (0.13 μmol/L) for 12 h or LPS (0.01 mg/mL) for 36 h, BACE1 protein and mRNA levels were significantly up-regulated (P<0.05). No significant changes were observed in the of BACE1 protein and mRNA of the PC12 cells treated with H2O2 (0.13 mmol/L or 0.25 mmol/L) for 12 h, under hypoxic or hypoglycemic environment (P>0.05). Conclusion · Mild ERS and inflammatory condition can up-regulate BACE1 mRNA and protein in PC12 cells.