Abstract: Soluble guanylate cyclase is a key signal transduction enzyme in the body, which can activate the NO-sGC-cGMP signaling pathway and inhibit the TGF-β signaling pathway. cGMP is one of the most important second messengers and also involved in a series of physiological or pathological responses including vasodilation, inhibition of platelet aggregation, inhibition of cell proliferation and so on. When TGF-β signaling pathway is inhibited, it can inhibit issue fibrosis and cell proliferation. Recent studies have shown that sGC can be activated directly to treat a variety of diseases. As a new class of potential drugs, sGC stimulators have shown many unique advantages. Herein, the mechanism and the latest research progress of sGC stimulators are reviewed, which could provide a useful information for further research of sGC stimulators.