Preliminary basic research and clinical ifndings have demonstrated that electroacupuncture ther-apy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level;there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we proifled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depres-sion-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vg f, Ig f2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to nor-malize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes.