We propose the application of early state photodynamic therapy (PDT) to treatment of atrial fibrillation, which is a kind of arrhythmia characterized by irregular rapid beating of heart. We had demonstrated that our PDT can block the propagation of electrical excitation in cardiac myocytes. However, the mechanism of the PDT-induced electrical blockade was not clear. In order to clarify this mechanism, changes in intracellular Ca2+ concentration during the PDT with Talaporfin sodium (water soluble photosensitizer) were measured by fluorescence Ca2+ indicator, fluo-4 AM. The PDT led to the rapid increase of intracellular Ca2+ concentration and the changes in cell shapes. These results indicated that extracellular Ca 2+ flowed into the cells mediated by cell membrane. Moreover, we found bubble generation in the cells after the PDT. In conclusion, the PDT-induced electrical blockade in myocytes can be caused by cell death following the bubble generation, which is accompanied by the increase in intracellular Ca2+ concentration due to the cell membrane malfunction with the PDT.