Objective:To study the effects of electroacupuncture on Yintang(EX-HN3)and Baihui(GV20)acupoints on the contents of second messengers cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP)in model rat of chronic stress depression,and reveal the possible mechanism of electroacupuncture in the treatment of depression. Methods32 Sprague-Dawley male rats were randomly divided into the normal control group,model group,electroacupuncture group and fluoxetine group,8 rats in each group. Except the normal control group,the rats in the other groups were raised separately and treated with the chronic unpredictable stress stimulation to establish the model. One day before and 21st day of after stress stimulation,the rats in each group were performed the open field test respectively,and the behavioral changes of rats were observed. The contents of cAMP and cGMP in hippocampus of rats were detected by radioimmunoassay.  Results:Compared with the normal control group,the horizontal and vertical movement of rats in the model group were significantly decreased(P<0.01),and the exploration ability of rats was decreased. Compared with the model group,the horizontal and vertical movement of rats in the electroacupuncture group and fluoxetine group were obviously increased(P<0.05),and the activity of rats was increased. Compared with the normal control group,the cAMP content was decreased and the cGMP content was increased in the model group,and the ratio of cAMP/cGMP was reduced,with statistically significant differences(P<0.01). Compared with the model group,the cAMP content was increased and the cGMP content was decreased in the electroacupuncture group and fluoxetine group,and the ratio of cAMP/cGMP was increased,with statistically significant differences(P<0.05).  Conclusion:Regulating the contents of cAMP and cGMP in central nervous system to balanced state is one of the possible mechanisms of electroacupuncture in the treatment of depression.