Abstract: The aims of this study were to identify the differences of glutathione antioxidant system responses in marine bivalves to the extractable and total contents of heavy metals in costal sediments, and to provide the information for screening suitable biomarkers reflecting the comprehensive toxicity of heavy metals. The speciation of Cu, Pb, Zn, Cd and Cr were measured in intertidal sediments from different sites along the Beibu Bay. In addition, w(GSH) (reduced glutathione content), w(GSSG) (oxidized glutathione content), GPx (glutathione peroxidase) activity, GST (glutathione S-transferase) activity,tGSH (total glutathione content), w(GSH)/w(GSSG) and OSI (oxidative stress index) in gills of Meretrix meretrix were determined or calculated. Results showed that the mean values were 13.40,1.93,3.19,0.09and 0.10mg/kg for w(TE-Pb) (extractable Pb), w(TE-Cr), w(TE-Cu), w(TE-Zn), w(TE-Cd), respectively. w(TE-Cd) accounted for 60.2%-98.1% of w(T-Cd) (total Cd), which was notably higher than its residual fraction, and composed mainly of water/acid soluble fraction and organic matter/sulphides fraction; higher percentages of w(TE-Pb) and w(TE-Zn) were observed at some sampling sites, on average accounted for 44.6% and 56.6% of the total contents; Cr and Cu were dominated by the residual fraction, the extractable forms counted for only 17.9% and 36.5% of the total on average. The spatial variation of extractable contents were consistent with that of the total contents for most of the metals except Cr. w(GSH) and w(GSSG) were 4.07-6.06,4.01-6.59mg/g respectively. The antioxidant factors significantly responded to both total contents and extractable contents of metals included w(GSSG) versus Cd, w(GSH)/w(GSSG) versus Cr and Cd, OSI versus Cr and Cd. However, w(GSH)/w(GSSG) and OSI were only affected by w(T-Zn), and GST activity was associated only with w(TE-Cu) and w(TE-Zn). There were significant differences in the responses of some antioxidant factors to total and extractable heavy metals. The results confirm that biomarkers for integrated sediment toxicity assessment can not be solely decided on the basis of the total content of heavy metals in the sediment.