The cyclic dinucleotides such as cyclic-di–guanosine monophosphate (c-di-GMP), c-di-AMP and cGAMP were discovered as second messengers in many species of bacteria, but weren’t identified in mammal.Recently, cGAMP was demonstrated to play critical regulatory roles as endogenous second messenger in mammal innate immune signaling. cGAMP can be catalyzed by cytoplasmic cGAMP synthase (cGAS) after DNA binding, and then bind to STING(stimulator of IFN genes) which triggers type I interferon-dependent innate immunity. These researches provide new perspective for signaling pathway in innate immunity and are beneficial for development of therapeutic agents in immune therapy.