Objective To investigate the effect and potential mechanisms of safflower yellow ( SY ) pigment against ischemia-reperfusion injury of rat isolated hearts and reduction of RIP3 nitration. Methods 36 SD male rats were randomly divided into 6 groups ( n=6 ) : normal control group ( group A ) , ischemia-reperfusion injury group ( group B ) , SY groups ( group C : 10 μmol/L , group D : 30 μmol/L , group E : 90 μmol/L ) , Edaravone group ( group F:10 μmol/L ) . At the end of reperfusion , the percentages of myocardial infarction area with TTC staining method were measures after reperfusion. The expression of RIP3 , RIP1 , N-RIP3 and P- RIP1 were measured by western blotting combine immune precipitation . Activity of SOD and content of MDA in myocardial tissue were measured with chemical colorimetry . Results At the end of reperfusion , compared with group B ( 36.3±4.7 ) % , area of myocardial infarction of group D (15.3±4.2) % , E (6.9±4.4 ) % , F (9.6±1.2) % decreased ( P < 0.05 ) . Compared with group B , SOD activity of myocardial tissue in group D , E , F group were increased ( P < 0.05 ) and MDA content were lower ( P < 0.05 ) . At the end of the reperfusion , there were no differences in expression of RIP3 and RIP1 in myocardial tissues ( P > 0.05 ) in each group . Compared with group B , the level of N-RIP3 in group D , E , F decreased ( P < 0.05 ) , the level of P-RIP1 in group D , E , F also decreased ( P < 0.05 ) . Conclusions SY protects ischemia-reperfusion injury of rat isolated heart by down-regulating oxidation level , decreasing the level of N-RIP3 and P-RIP1 .