Acupuncture is increasingly being used as a complementary therapeutic approach, but its efficacy remains controversial and the physiological mechanisms determining its actions are largely unknown.

To explain the existence of the acupoints there were published a lot of studies, searching a visual method to explain the meridians. In 1984 Dung observed that there were no particular structures under the acupoints, but he saw that nerve bundles were involved in almost all such locations. In 1996, with a study based on histological analysis, Croley showed that in the area of acupuncture points there were high concentration of dermal papillae containing capillary loops with sympathetic nerve endings. Helene Langevin has also shown, by the histochemical examination, how subtle differences in acupuncture-needle manipulation techniques can affect cellular responses in mouse subcutaneous connective tissue.

The recent neuroimaging trials found altered functional brain responses to acupuncture in sensory, affective, cognitive, and inhibitory regions, often including neural networks for pain perception and transmission. These discoveries have allowed a better understanding of the functioning of acupuncture against diseases. Napadow in 2010 monitored the acupuncture effects on human brain with functional MRI, and he showed how acupuncture mobilizes a limbic-paralimbic-neocortical network and its anti-correlated sensorimotor/paralimbic network at multiple levels of the brain.

Furthermore, it's now sure that acupuncture has numerous endocrine and neurotransmitter effects. After Han's work, many authors have reported activation of endogenous opioid peptide related antinociceptive pathways during acupuncture, which involves the arcuate nucleus, the peri-aqueductal gray, the nucleus raphe magnus, and the descending inhibitory pathways. In 2014, Wu localized ATP release at acupoints after acupuncture, demonstrating that acupuncture is related to neural regulation based on ATP.

Thomas in 2008 showed how acupuncture can reduce the oxidative damage in pathological conditions, Wang discovered that it can exert an antiapoptotic effect through regulating the expression of genes Bax and Bcl-2. All these and some more recent studies confirmed that acupuncture has local and systemic effects mediated by nervous and neuro-endocrine-immune systems, but its mechanisms are still far from being fully understood.