Abstract: To obtain the optimum condition of high -hydrostatic pressure on Vibrio parahaemolyticus (Vp) , two strains, CDC-1 (clinical isolates, O3:K6 serotype) and CGMCC1.1997 (reference strain, O1:K1 serotype) were used in this study. Their resistances to high pressure were investigated and the resistances of CDC-1 strains in live oysters and in oyster homogenates was also tested. Results showed that there was an obvious reduction of Vp in oyster homogenates at pressure levels of ≥200MPa, and HPP was proved to be an efficient means of reducing Vp in oysters. Increasing pressure and extending time could enhance inactivation of Vp. Multiple demonstrated that there were significant differences between the CDC-1 strain and the CGMCC1.1997 strain (p <0.05) , and the CDC-1 strain had higher resistance to HPP. Resistance variations of CDC-1 strain were detected in live oysters and in oyster homogenates (p<0.05) , the CDC-1 strain was of higher resistant to HPP in oyster. To inactivate the Vp in oyster pressure treatment needed to be conducted at pressure levels of 300MPa for 10min or 350MPa for 5min.