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 (P0.05). The linear effects of salinity on SOD and CAT activities were significant (P0.05), but the linear effect of salinity on GSH-PX activity was not significant (P0.05). Salinity had significant quadratic effect on SOD, CAT and GSH-PX activities (P0.05). The interactive effects of temperature and salinity were significant on SOD and CAT activities (P0.05), but there was no significant effect on GSH-PX activity (P0.05). By response surface methodology, we established a model equationfor the relationship of antioxidant enzyme activities to the two factors, with the R2of 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 Umg-1, 35.73 Umg-1 and 27.94 Umg-1) when the 2-factor combination was 26.4 ℃/27.7, with the desirability value being 0.989.