This article explores the mechanisms of acupuncture meridians by determining characteristics of the tissue fluid flow in the connective tissue along meridians. Based on deep dissection of acupoints on the upper and lower limbs of the human body and micro and macro observation and measurement, a mathematical model of the flow of tissue fluid in interosseous membranes is constructed. It is shown that the signal transmission along acupuncture meridians may be determined by unique anatomical and physiological factors that govern the flow of tissue fluid in the connective tissue and involve mast cell degranulation. Our results provide a preliminary explanation of the phenomenon of the "de qi" sensation and the mechanism of acupuncture signal transmission along acupuncture meridians.