Purpose: Acupuncture has been used to relieve stress.Although recent studies have shown that acupuncture can reduce stress, its mechanism remains unclear.The present study investigated the effect of acupuncture on immobilization stress-induced neuroinflammation in the rat hypothalamus.Methods: Rats were immobilized for 60 min.Manual acupuncture was performed at HT7 during the immobilization period.Gene expression of several pro-inflammatory factors and serum level of stress hormone and PGE2 were evaluated using real-time PCR and ELISA, respectively.Results: The stress-alleviating effect of acupuncture was confirmed by inhibiting hypothalamic CRF mRNA expressions as well as serum corticosterone levels in response to immobilization stress.The mRNA expression of pro-inflammatory mediators including TNF-␣ and IL-1 in the hypothalamus increased significantly after immobilization stress.Acupuncture treatment at HT7 during the immobilization significantly suppressed the immobilization stress-induced increase of pro-inflammatory mediators in the hypothalamus.Also, acupuncture inhibited significant increases in hypothalamic COX-2 mRNA as well as serum PGE2 levels in response to immobilization stress.Conclusion: These data clearly suggest a stress-relieving effect of acupuncture and the inhibition of neuroinflammation as a possible action mechanism for its anti-stress effect.