Non-specific connective tissue (fascia connective tissue) plays an important role in the mechanical signal transduction of acupuncture. Acupuncture needle manipulation-induced mechanical stress has a certain effect on the fibroblasts and cytoskeleton in the nonspecific connective tissue (including loose connective tissue and fat tissue) in morphology, histochemistry and biochemistry. For example, acupuncture-needle manipulation can make the fibroblast deformed, the cytoskeleton remodeled and result in the release of biochemical materials from the connective tissue. The present review summarizes new results of studies on the effect of acupuncture needle manipulation from cytobiology, imageology and physiology; and holds that making clear the transduction pathways of acupuncture mechanical stress signals in the connective tissue and its impact on the organism possesses an important significance in revealing the mechanism of acupuncture underlying clinical therapeutic effects.