〔Abstract〕 Objective To observe the level of intracellular free Ca2+in cortex and hippocampus of epileptic rats and the effect of low dose gamma knife irradiation on it. Methods 32 Wistar rats were randomly divided into four groups: ① Normal control group; ② gamma knife(GK) control group; ③ pentylenetetrazole(PTZ) group; ④ PTZ+GK group. Epileptic rat model was prepared by continuous intraperitoneal injection of PTZ. Leksell gamma knife system was used to irradiate rats with low dose gamma knife for 12 weeks. The target area was bilateral frontal lobe. On the 12 th week after gamma knife irradiation,the brains of rats were decapitated and neurons of frontal lobe and hippocampus were acutely isolated. The neuron cell suspension was prepared,and then laser scanning confocal microscopy(LSCM) was used to detect the level of free Ca2+in nerve cells. Results Compared with the normal control group,the fluorescence intensity of Ca2+in cortex and hippocampal neurons of PTZ group increased significantly(P<0.05). Compared with PTZ group,the fluorescence intensity of Ca2+in neurons of PTZ+GK group decreased markedly(P<0.05). The fluorescence intensity of Ca2+in neurons of GS control group was slightly higher than that of normal control group,but the difference was not statistically significant(P>0.05). Conclusion The increased Ca2+level of neurons in frontal cortex and hippocampus may be one of the important mechanisms of epilepsy. Low dose of gamma knife irradiation may play a role of anti-epileptic and improve cognitive function by affecting intracellular calcium homeostasis.