To better understand the therapeutic effectiveness of acupuncture, questions about the underlying mechanisms need to be addressed. Here we describe the impact of manual stimulation by an acupuncture needle of zusanli (stomach 36 [ST36]) on analgesia in rats. The analgesic effect was more pronounced after stimulation of ST36 than after stimulation of a sham point near the acupuncture point. At the same time, we determined in tissue slices the density of mast cells in the acupuncture points and nearby points, as well as the degree of degranulation before and after stimulation. We found that the density of mast cells from the ST36 of rats was higher than that from a nearby sham point. In addition, acupuncture resulted in a remarkable increase in degranulation of the mast cells. Pretreatment of the acupuncture point with disodium chromoglycate not only counteracted the phenomenon of degranulation but also reduced analgesic effect of acupuncture. Our experiments on inhibition of degranulation of mast cells in tissue from acupuncture points demonstrates the possible role of mast cells in acupuncture effects.