Norepinephrine (NE) and acetylcholine (ACh) are important neurotransmitters of sympathetic and parasympathetic nerves, which play antagonistic roles in regulating different islet hormones secretion. Phosphorylation is reported as a critical post-translational modification participates in neural regulation on various physiological activities in islet. However, the molecular mechanisms of these two transmitters in islet are unknown and whether the neuronal regulation is abnormal in diabetes mellitus also unclear. Quantitative phosphoproteome analysis were performed on murine islet after short time stimulation with neurotransmitters NE and ACh to reveal the key moleculars and phosphorylated proteins in islet which participate in the innervation of nerve signaling.