Aim Snake venom polypeptide X was isolated from Naja naja atra snake venom, its Ca 2+ antagonizing effect on formation of foamy macrophages was explored in these studies. Methods Foam like cells were induced by C57BL/6J mouse peritoneal macrophages incubated with 10 mg/L oxidized low density lipoprotein, and their intracellular Ca 2+ levels influenced both slowly and instantly by snake venom polypeptide X were determined with the Ca 2+ fluorescent indicator technique. Results The average intracellular Ca 2+ level of the foam like cells in 10 mg/L snake venom polypeptide X was 40.2% of the control(P<0.05); While the instant influence of snake venom polypeptide X on the Ca 2+ level was not considerable. Conclusions Snake venom polypeptide X exerted an antagonizing role to the increasing intracellular Ca 2+ level, thus prevented the macrophage derived foam cell formation.