As for an important central regulatory neurotransmitter involving acupuncture effect, serotonin (5-HT) is worthy of being paid with more attention. In the present paper, the authors review development of researches on the involvement of 5-HT and its receptor subunits in pain perception, acupuncture analgesia, and other effects of acupuncture (anti-depression, weight-reduction, etc.). Many studies showed that acupuncture intervention could modulate the content and activity of central 5-HT, and these changes varied under different conditions. Hence, the relationship between 5-HT and other neurotransmitters in acupuncture analgesia and its different functions in different regions of the central nervous system should be considered comprehensively.