OBJECTIVE To observe the effect of electroacupuncture (EA) on the related hormones of the hypothalamus-pituitary-adrenal (HPA) axis in rats with cerebral ischemia-reperfusion injury (CI-RI). METHODS Ninety Wistar rats were randomly divided into normal control, sham-operation (sham), model, EA acupoint and EA non-acupoint groups. CI-RI model was established by using modified middle cerebral artery occlusion (MCAO) and reperfusion. These rats were further divided into 1 day (d), 3 d and 7 d subgroups, with 6 cases in each. EA (1 mA, 2 Hz/30 Hz) was applied to acupoint "Zusanli" (ST 36) and "Quchi" (LI 11), and non-acupoints (5 mm lateral to ST 36 and 5 mm apart from LI 11 on the radial side respectively) for 30 min, once daily for 1 d, 3 d and 7 d separately. Serum cortisole (CORT) content was assayed by enzyme linked immunosorbent assay (ELISA), and the expression of hypothalamic adrenocorticotropic releasing factor (CRF) mRNA and glucocorticoid receptor (GR) mRNA, and pituitary adrenocorticotrophic hormone (ACTH) mRNA was assayed by reverse transcription polymerase chain reaction (RT-PCR) method. RESULTS Compared with normal and sham groups, serum CORT levels of model and EA non-acupoint groups on the 1st, 3rd and 7th day increased significantly (P < 0.05), while compared with model groups, serum CORT level of EA acupoint groups decreased apparently (P < 0.05). Compared with normal and sham groups, hypothalamic CRF mRNA and pituitary ACTH mRNA expression of model groups were upregulated significantly on the 1st, 3rd and 7th d after CI-RI (P < 0.01, P < 0.05), and hypothalamic GR mRNA expression of model groups were obviously downregulated (P < 0.01, P < 0.05). In comparison with model groups, hypothalamic CRF mRNA and pituitary ACTH mRNA expression of EA acupoint groups at the 3 time-points, and their expression of EA non-acupoint groups on the 1st and 3rd day were remarkably downregulated (P < 0.01, P < 0.05), and hypothalamic GR mRNA expression of EA acupoint groups was upregulated significantly at the 3 time-points (P < 0.01, P < 0.05). Comparison between EA acupoint and EA non-acupoint groups showed that the effect of EA acupoint groups was obviously superior to that of EA non-acupoint groups in downregulating CRF mRNA and ACTH mRNA expression and in upregulating GR mRNA expression at the 3 time-points (P < 0.01, P < 0.05). CONCLUSIONS EA of meridian-acupoints can effectively downregulate serum CORT content, hypothalamic CRF mRNA and pituitary ACTH mRNA expression and upregulate hypothalamic GR mRNA expression in CI-RI rats, which may contribute to its effect in relieving CI-RI.