Pain remains challenge to treat, despite advances in cellular and molecular understanding of pain. Acupuncture analgesic has been accepted by west society due to low side effect and good performance. Although the effect of acupuncture analgesic has been confirmed clinically, its mechanism is still unclear. Positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and immunohistochemistry have been applied in the study of the mechanism of acupuncture analgesic. However, poor resolution or invasion of these techniques limits their application in further study. It is suggested that optical imaging techniques, especially laser scanning confocal microscopy, optical coherent tomography and in vivo optical imaging system, could be utilized in the study of the mechanism of acupuncture analgesic.