The nitric oxide-cyclic GMP(NO-cGMP) signaling system mediates important physiological functions associated with various integrative body systems.Massive researches show that NO –cGMP signaling plays an important role in inducing the stem cells into the myocardial cell,neuron,etc.Besides,NO – cGMP signaling can also promote the axonal elongation.This review focuses on the role of NO-cGMP signaling in the differentiation of stem cells such as embryonic stem cells(ESCs),mesenchymal stem cells(MSCs) and neural stem cells(NSCs).