Objective To investigate the protective effects and the mechanisms of 17β-estradiol on the propofol-induced neuroapoptosis in primary cultured rat cortical neurons. Methods The neurons were cultured for 7 days and then divided into three groups:vehicle-control group(treated with equal volume of 20% intralipid), propofol-treated group(treated with 500μmol/L propofol), and propofol plus 17β-estradiol treated group(treated with 500μmol/L propofol and 0.1μmol/L 17β-estradiol). 12 hours after the treatment, neuroapoptosis was detected by Hoechst 33258 staining and TUNEL assay, and the levels of Bcl-2, Bax and cleaved caspase-3 proteins were detected by Western blot. Results Compared with the vehicle-control group, the neuroapoptosis increased greatly(P<0.01), Bcl-2 level reduced(P<0.01), Bax and cleaved caspase-3 levels increased greatly(P<0.01), and Bcl-2/Bax ratio reduced significantly(P<0.01). Compared with the propofol-treatment group, the neuroapoptosis decreased greatly(P<0.01), Bcl-2 level increased(P<0.01), Bax and cleaved caspase-3 levels reduced greatly(P<0.01), and Bcl-2/Bax ratio increased greatly(P<0.01). Conclusions 17β-estradiol can protect cortical neurons against propofol-induced cortical neuroapoptosis by regulating the expression of Bcl-2 and Bax.