Abstract: By using two-factor central composite design (CCD) and response surface methodology(RSM), we studied the synergistic effect of temperature (19~31 ℃) and salinity (22~38) on the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) activities of Chlamys nobilis. The results show that the linear and quadratic effects of temperature on SOD, CAT and GSH-PX activities were significant (P < 0.05). The linear effects of salinity on SOD and CAT activities were significant (P < 0.05), but the linear effect of salinity on GSH-PX activity was not significant (P>0.05). Salinity had significant quadratic effect on SOD, CAT and GSH-PX activities (P < 0.05). The interactive effects of temperature and salinity were significant on SOD and CAT activities (P < 0.05), but there was no significant effect on GSH-PX activity (P>0.05). By response surface methodology, we established a model equation for the relationship of antioxidant enzyme activities to the two factors, with the R² of 0.950 1, 0.981 5 and 0.967 9. It is suggested that the fitting capability of the model was satisfactory and could be practicably applied for prediction. The antioxidant enzyme activities reached their maximum (33.02 U · mg^-1, 35.73 U · mg^-1 and 27.94 U · mg^-1) when the 2-factor combination was 26.4 ℃/27.7, with the desirability value being 0.989.