Objective To investigate the role of GDNF-PI3K-Akt signal transduction pathway in the treatment of functional constipation with electroacupuncture at large intestine Shu and Mu acupoint. Methods Ten wild mice were used as control group. Thirteen GFRα1 knockout mice were randomly divided into model group and acupuncture group. The model group and the acupuncture group mice were treated with 10 mg/（ kg·d） 10 mg/（ kg·d） for 14 days to establish a functional constipation mouse model. After acupuncture

acupuncture mice were given the left side Tianshu（ ST25） and left Dachangshu（ BL25） on the first day of electroacupuncture. On the 2 nd day

the electroacupuncture points of the right side were alternated

and the needles were alternated for 30 minutes each time for 5 consecutive days. The control group and model group did not receive any treatment. The gastric emptying rate and small intestine advancing rate were observed in mice in each group. The expression of glial cell line-derived neurotrophic factor（ GDNF）

Rai

tyrosine kinase receptor（ RET） protein and its mRNA in distal colon tissue were detected. The content of PI3K and Akt protein in the distal colon tissue was detected. Results Compared with the control group

the gastric emptying rate and intestinal propulsion rate in the model group decreased

and the expression of Rai protein and mRNA in the distal colon decreased. The expression of RET protein decreased

and the expression of PI3K and Akt protein increased（ P < 0. 05 or P < 0. 01）. Compared with the model group

there was no significant difference in gastric emptying rate

small intestine advancing rate

GDNF

Rai

RET protein and mRNA expression in the acupuncture group（ P > 0. 05）

and PI3K and Akt protein expression was down-regulated（ P < 0. 05）. Conclusion The GDNF-PI3K-Akt signal transduction pathway may be the main route of electroacupuncture at the point of large intestine shu to treat functional constipation.