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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 Western blotting after 107. 10−6 and 106 mol/L of CORT was added to culture medium. The evident effect of 10−6 and 105 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], increased in the neurons treated with 106 and 105 mol L of CORT, but no change was observed in the neuron treated with 106 mol/L of CORT. The death was either by way of apoptosis or necrosis in the cells treated with 106 and 105 mol/L of CORT respectively. The correlation analysis showed that a reverse correlation existed between [Ca2+], and the expression of CaMK II. Either apoptosis or necrosis occurs in the hippocampal neurons treated with CORT. The increased hippocampal [Ca2+], is both the results of CORT impairing the hippocampal neurons and the cause of the apoptosis of hippocampal neurons and the decreased CaMK II expression. [ABSTRACT FROM AUTHOR]