There have been many studies of electro-acupuncture analgesia (EAA), but whether EAA develops mainly on the stimulated meridians or irrespective of these meridians has not yet been clarified. We evaluated the association between endogenous analgesia (plasma β-endorphin), and meridians in electro-acupuncture of the large intestine meridian of the hand-yangming LI4 (Hegu, Gokoku) point. LI4 electro-acupuncture resulted in EAA on the meridians associated with LI4, other meridians, and acupuncture points in the forehead glabella (Yintang, Indou), abdomen CV 12 (Chungwan, Chukan), and crus ST36 (Zsusanli, Ashi no Sanri) point. Simultaneously, LI4 electro-acupuncture significantly increased plasma β-endorphin level. These results suggest that analgesia observed after LI4 electroacupuncture is not associated with meridians, and is caused by the increases in the plasma β-endorphin level.