OBJECTIVE To investigate the protective effect of calcium antagonists (A/R) injury of cardiomyocytes. METHODS Primary-cultured cardiomyocytes were divided A/R, A/R+nicardipine(Nic), A/R+HOE642, A/R+H7, A/R+PD98059 and control parameters were measured in all groups, intracellular calcium concentration ([Ca2+]i), content, lactate dehydrogenase (LDH) and creative phosphokinase(CK) activity in the activity. The calpain (u-calpain and m-calpain) protein expression levels were measured In comparison with A/R group, A/R + nicardipine (Nic) and A/R + Nic groups showed [Ca2+]i, m-calpain protein expression, LDH and CK content in the medium, a higher activity of PKC and MAPK (P < 0.01). On the contrary, A/R+H7 and A/R+PD98059 LDH and CK content in the medium, and lower ATP content and cell viability as compared 0. 05). CONCLUSIONS The A/R mediated Ca2+ overload resulting from cardiomyocyte injury blocking Ca2+ entry and H+/Na+ exchange, and very likely PKC and MAPK are involved protection against the A/R injury of cardiomyocytes.