This study was designed to investigate the effect and molecular mechanisms of Haishengsu (HSS), a protein extract from a shellfish Tegillarca granosa L., on a drug resistant leukemia cell line. Cultured K562/adriamycin (ADM) cells were treated with HSS at 10, 20 and 40 'g/ml, respectively. The apoptosis and expression of p-glycoprotein was evaluated by flow cytometry. Expressions of caspase-3 and bcl-2 were also evaluated. There was a significant dose-dependent increase in the apoptosis in the HSS treated K562/ADM cells (P<0.05 and 0.01, respectively). The p-glycoprotein expression in the 40 'g/ml HSS group (14.8%) was lower than in the control (16.9%, P<0.05) and the 10 'g/ml HSS group (7.3%, P<0.05), but it was similar to the HSS 20 'g/ml group (10.7%, P>0.05). The expressions of apoptosis-stimulating protein caspase-3 protein were increased, whereas the expressions of apoptosis-suppressing bcl-2 were decreased in the HSS groups, as compared with the levels in the control group (P<0.05). We conclude that HSS induces apoptosis of the adriamycin-resistant K562/ADM cells. The enhanced expressions in caspase-3 and the reduced expressions in bcl-2 protein may have contributed to the apoptosis-stimulating effect of HSS. The inhibition of p-glycoprotein suggests that HSS may diminish the resistance to adriamycin and potentially enhance the therapeutic effects.