Objective To explore the possible mechanism of needling points group of Yintang（ EX-HN3）-Baihui（ DU20）-Fengchi（ GB20）-Shenshu（ BL23） in treating depression. Methods Forty Sprague Dawley（ SD） rats were randomized into normal group

model group

needling group and the western medicine group

with 10 rats in each group. Rats in the normal group were fed normally. Rats in other groups were fed alone and were made chronic stress rat models by 28 days of unpredictable chronic stress stimuli. At the same time of modeling

the model group was given normal saline 2 ml by gavage every day. The needling group was given 30 minutes of acupuncture treatment in Yintang（ EX-HN3）

Baihui（ DU20）

bilateral Fengchi（ GB20） and bilateral Shenshu（ BL23） once every day. The western medicine group was given fluoxetine capsule 0. 18 mg/（ kg ·d） by gavage once every day.Rats in other groups were treated by gavage for 28 days except the normal group. It was detected that rats’ hippocampus brain-derived neurotrophic factor（ BDNF）

adenosine cyclophosphate responsive element-binding protein（ CREB） mRNA level

as well as the methylation levels of hippocampus BDNF I-17 locus gene and BDNF I-17 Cp G6 locus gene. Results Compared with the normal group

rats’ hippocampus CREB and BDNF mRNA level in the model group decreased（ P < 0. 05 or P < 0. 01）. Compared with the model group

rats’ hippocampus CREB and BDNF mRNA level in the needling group and the Western medicine group increased（ P < 0. 05）. The difference of methylation levels of rats’ BDNF I-17 locus in all groups was not significant（ P > 0. 05）. The methylation level of rats’ BDNF I-17 Cp G6 locus in the model group was lower than that in the normal group（ P < 0. 05）; the difference among other groups was not significant. Conclusion Needling points group of Yintang-Baihui-Fengchi-Shenshu might increase the levels of chronic stress model rats’ hippocampus CREB and BDNF mRNA

which might be one of the mechanisms of treating depression.