Objective To observe the changes of behavior, intracellular free calcium and the expression of calmodulin dependent protein kinase Ⅱ(CaMKⅡ) in the hippocampal neurons of chronic forced swimming stress rats. Methods Male Wistar rats were randomly divided into control group and chronic forced swimming stress group. The behavior was examined using sucrose preference test, open-filed test and Morris water maze. The intracellular free calcium was examined by fluorescence spectrophotometer. The expression of CaMKⅡ was detected using colloidal gold immunoelectron microscopy technique, Western blotting and RT-PCR. Results The consumption of sucrose and erect quantity of chronic forced swimming stress group were lower than those of control group（EM>P/EM><0.01, EM>P/EM><0.05）. The escape latency time in Morries water maze test of chronic forced swimming stress group was higher than that of control group（EM>P/EM><0.01）. The intracellular free calcium level and the expression of CaMKⅡ in the hippocampus was higher than that of control group（EM>P/EM><0.01）.Conclusion The lasting dys