Objective: To compare the regulatory effects of electro-acupuncture (EA) at acupoints Zusanli (ST36) and Hegu (LI4) on the visceral hyper-sensitivity in the rat model of irritable bowel syndrome (IBS), and to explore the acting targets and specialty of acupoints. Methods: Except 8 rats of the normal control group, the rest 32 rats were prepared to set up the IBS models. IBS animal model was prepared by enema with acetic acid. Model rats were divided into three groups. Except for rats in the model group for control, those in the other two groups were treated 20 min by EA on ST36 (EA-ST36) and LI4 (EA-LI4) respectively for 2 weeks to observe the effect on behavior response of viscera sensitivity. The changes of neuropepUde (NPY), the somatostatin (SS) levels in blood and tissues of brain and intestine were monitored as well. Results: The volume thresholds for abdomen uplifting and beck hunching were obviously increased after EA-ST36 (P〈0.05), but showed insignificant change after EA-LI4. NPY contents lowered and SS contents increased in model rats; both EA-ST36 and EA-LI4 could raise the level of thalamic NPY (P〈0.01 and P〈0.05, respectively), but showed insignificant effects on NPY in colonic tissue. As for SS content, its colonic level could be reduced by EA-S36 and EA-LI4 (P〈0.01 and P〈0.05, respectively), however, its blood level was affected only by EA-ST36 (P〈0.05). Conclusions: EA-ST36 or EA-LI4 could regulate the NPY in thalamus and SS in colonic tissue, the former could affect blood level of SS as well. It is deemed that NPY and SS may be the key substances for regulating the action of acupuncture in the braln-intastinal axis; their different levels could be regarded as an indicator for the functional differenca between the acupoints.