Aim To elucidate the effect of low osmotic contrast medium ioxaglate and iso-osmotic contrast medium iodixanol on platelet and leukocyte activation. Methods Hirudinized whole blood was incubated with 0%,2%,5% and 10% concentrations of ioxaglate or iodixanol at 37℃ for 5 min.Whole blood flow cytometric method was used to measure P-selectin,marker of platelet activation,CD11b,marker of leukocyte activation,and platelet-leukocyte aggregates.Blood samples were also incubated with collagen with stirring to investigate the impact of contrast medium(5% of ioxaglate or iodixanol) on platelet-leukocyte cross-talk. Results Ioxaglate had no effect on P-selectin expression of un-stimulated samples(P>=0.237),whilst iodixanol mildly increased P-selectin expression(P><0.01);However,both contrast media remarkably decreased 1 μmol/L adenosine diphosphate(ADP)-induced P-selectin expression(P><0.001),and ADP-stimulated platelet-leukocyte aggregates(P><0.001).Ioxaglate had effect on neither resting nor 0.1 μmol/L N-formyl-methionyl-leucyl phenylalanine(fMLP)-stimulated CD11b expression,whilst iodixanol mildly increased both resting and 0.1 μmol/L fMLP-stimulated CD11b expression(P><0.05).Ioxaglate inhibited collagen-stimulated platelet-induced CD11b expression(P><0.05),whilst iodixanol had no impact on platelet-leukocyte cross-talk.Both ioxaglate and iodixanol markedly reduced collagen-stimulated platelet-leukocyte aggregates(P><0.01). Conclusion Both ioxaglate and iodixanol can reduce ADP-stimulated P-selectin expression and platelet-leukocyte aggregates.Yet,iodixanol slightly increases resting P-selectin expression,and both resting and fMLP-stimulated CD11b expression.As far as the influence on platelet and leukocyte activation is concerned,ioxaglate is safer than iodixanol when used clinically.