To explore the effect of different concentrations of corticosterone (CORT) on primary cultured hippocampal neurons and their Ca2+/CaMK Ⅱ expression and possible mechanism, the changes of hippocampal neurons were observed in terms of morphology, activity of cells, cell death,concentrations of cytosolic free calcium, and the expression of CaMK Ⅱ by using MTT assay, flow cytometry, fluorescent labeling of Fura-2/AM and West blotting after 10-7, 10-6 and 10-5 mol/L of CORT was added to culture medium, The evident effect of 10-6 and 10-5 mol/L of CORT on the morphology of hippocampal neuron was found. Compared with control neurons, the activity of the cells was markedly decreased and [Ca2+]i increased in the neurons treated with 10-6 and 10-5mol/L of CORT, but no change was observed in the neuron treated with 10-7 mol/L of CORT.The death was either by way of apoptosis or necrosis in the cells treated with 10-6 and 10-5 mol/L of CORT respectively. The correlation analysis showed that a reverse correlation existed between[Ca2 ]i and the expression of CaMK Ⅱ. Either apoptosis or necrosis occurs in the hippocampal neurons treated with CORT. The increased hippocampal [Ca2+ ]i is both the result of CORT impairing the hippocampal neurons and the cause of the apoptosis of hippocampal neurons and the decreased CaMK Ⅱ expression.