第二信使（英语：Second messenger）在生物学里是胞内信号分子，负责细胞内的信号转导以触发生理变化，如增殖，细胞分化，迁移，存活和细胞凋亡。因此第二信使是细胞内的信号转导的启动组成部件之一。第二信使分子的例子包括：环腺苷酸（cAMP），环磷酸鸟苷（cGMP），肌醇三磷酸（IP3），甘油二酯（DAG），钙离子（Ca）。细胞释放第二信使分子是响应于暴露在细胞外的信号分子-第一信使。第一信使是细胞外因子，通常是激素或神经递质，如肾上腺素，生长激素，和血清素。

厄尔·威尔伯·萨瑟兰（Earl Wilbur Sutherland Jr.）发现的第二信使，为他赢得了1971年诺贝尔生理学或医学奖。萨瑟兰看到，肾上腺素会刺激肝脏把肝细胞的糖原转化为葡萄糖（糖），但肾上腺素单独不会糖原转化成葡萄糖。他发现，肾上腺素必须触发一个第二信使，环磷酸腺苷，才把肝脏的糖原转化为葡萄糖。该机制被马丁·罗德贝尔（Martin Rodbell）和艾尔佛列·古曼·吉尔曼（Alfred G. Gilman）详细研究，他们赢得了1994年诺贝尔生理学或医学奖。

Second messengers are intracellular signaling molecules released by the cell to trigger physiological changes such as proliferation, differentiation, migration, survival, and apoptosis. Secondary messengers are therefore one of the initiating components of intracellular signal transduction cascades. Examples of second messenger molecules include cyclic AMP, cyclic GMP, inositol trisphosphate, diacylglycerol, and calcium. The cell releases second messenger molecules in response to exposure to extracellular signaling molecules—the first messengers. First messengers are extracellular factors, often hormones or neurotransmitters, such as epinephrine, growth hormone, and serotonin. Because peptide hormones and neurotransmitters typically are biochemically hydrophilic molecules, these first messengers may not physically cross the phospholipid bilayer cell membrane to initiate changes within the cell directly—unlike steroid hormones, which usually do. This functional limitation necessitates the cell to devise signal transduction mechanisms to transduce first messenger into second messengers, so that the extracellular signal may be propagated intracellularly. An important feature of the second messenger signaling system is that second messengers may be coupled downstream to multi-cyclic kinase cascades to greatly amplify the strength of the original first messenger signal. For example, Ras.GTP signals link with the Mitogen Activated Protein Kinase (MAPK) cascade to amplify the allosteric activation of proliferative transcription factors such as Myc and CREB.