To study the role of the arcuate nucleus of hypothalamus in analgesic action of l-tetrahydropalmatine (l-THP).The horseradish peroxidase (HRP) retrograde tracing, HRP retrograde tracing combined with immunohistochemistry, lesion of nucleus, tail-flick test, and intra-PAG injection were used in the present study.HRP retrograde tracing results showed that the striatum or accumbens nucleus connect with PAG by two pathways: 1) striatum or accumbens nucleus-->arcuate nucleus-->PAG; 2) striatum or accumbens nucleus-->habenula-->PAG. It was found that neurons in the arcuate nucleus projecting to PAG were mainly beta-endorphin neurons as observed by HRP retrograde tracing combined with immuno-histochemistry. After lesion of the arcuate nucleus, the analgesic action of l-THP (40 mg.kg-1, i.p.) was abolished, while lesion of the habenula had no such effect. Moreover, intra-PAG injection of naloxone (2, 3 micrograms) could markedly attenuate the analgesic action of l-THP (40 mg.kg-1, i.p.) in a dose-dependent manner.beta-Endorphin neurons in the arcuate nucleus play an important role in the analgesic action of l-THP.