Update information. The pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct LC-MS/MS based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over time with a boost in expression were enriched in lipase activity, lipoprotein and lipids absorption and transport regulation. Furthermore, 16 proteins associated with lipid metabolism and signaling pathways together with the whole lipid species changing profile led to the vital identification of changing law in glycerides, phosphoglycerides and free fatty acids. In addition to lipid metabolism and regulation associated proteins, several digestive enzymes and adaptive anti-trypsin, stress response, and energy metabolism related proteins showed an increment in abundance. Notably, central carbon and branched chain amino acids metabolism were enhanced during 0-24 h from the first cerulein stimulation. Taken together, this integrated proteomics and lipidomics revealed a novel metabolic insight on metabolites transforming rules that might be relevant to their function and drug targets investigation.