Objective To explore the possible mechanism of antidepressant effects of electroacupuncture at di-fferent intervention times on the miRNA level. Methods A total of 50 Wistar rats were divided into a normal group（n=10）

a model group（n=10）

a fluoxetine group（n=10） and a electroacupuncture group（n=20） by random number table method. Except for the normal group

chronic unpredictable mild stress was used for 28 days to construct a chronic stress depression rat model. At the same time of modeling

rats in the fluoxetine group were given fluoxetine tablets 20 mg/（kg·d） by gavage; rats in the electroacupuncture group were given electroacupuncture with "Yintang" and "Baihui" for 4 weeks. Before stress and after 2 and 4 weeks of intervention

rats in each group were subjected to sugar water preference experiment and forced swimming experiment. In the electroacupuncture group

10 rats were selected to take the hippocampus after 2 weeks and 4 weeks of intervention respectively

and rats in the normal group and model group were taken from the hippocampus after 4 weeks of intervention. Gene chip microarray analysis and quantitative real-time polymerase chain reaction were used（QRT-PCR） to detect the expression diffe-rences of miRNA（miR-383-5 p

miR-764-5 p

miR-675-3 p） in hippocampus

and bioinformatics detection methods was used to discover its regulated target genes and enriched signal pathways. Results After 2 and 4 weeks of intervention

the sugar water preference of the model group was significantly lower than that of the normal group

and the time of forced swimming immobility was significantly higher than that of the normal group（P<0.01）. After 4 weeks of intervention in the fluoxetine group and 2 and 4 weeks in the electroacupuncture group

the rats′ sugar preference and forced swimming immobility time were improved compared with the model group（P<0.05 or P<0.01）. After gene chip analysis and qRT-PCR detection

compared with the model group

the expression of miR-675-3 p in the hippocampus of rats in the electroacupuncture group was up-regulated（P<0.01） after 2 weeks of intervention

and the regulated target genes mostly involved GABAergic synapse

Dopaminergic synapse and PI3 K-Akt signaling pathway and other signaling pathways; miR-383-5 p

miR-764-5 p expression was down-regulated after 4 weeks of intervention（P<0.05 or P<0.01）

involving MAPK signaling pathway

neurotrophin signaling pathway etc. Conclusion The electro-acupuncture treatment of depression may stimulate different miRNAs and target genes related to the physical symptoms and psychological disorders of depression in different time courses.