Objective To investigate the effect of chaiqin chengqi decoction (CQCQD) on serum lipid metabolism in experimental acute pancreatitis. Methods A total of 27 C57BL/6 mice were randomly divided into three groups (n=9 for each group). The mice in the acute pancreatitis model group (AP group) and the acute pancreatitis model + CQCQD treatment group (APQ group) received seven intraperitoneal injections of cerulein (50 µg/kg) at hourly intervals, while the mice in the control group (CON group) received phosphate-buffered saline injections at the same regimen of cerulein. Oral gavage of CQCQD (5.5 g/kg) or same volume of distilled water was commenced 1 h after the first cerulein injection for three times at intervals of 4 h for the APQ group and AP group, respectively. Animals were sacrificed 12 h after the first cerulein / phosphate-buffered saline injection for collecting serum and tissue samples. The levels of serum lipase and amylase, pancreatic histopathology assessment, as well as pancreatic myeloperoxidase activity, were used to assess the severity of acute pancreatitis and the efficacy of CQCQD. Additionally, serum lipid metabolites were analyzed in all groups. Results In comparison to the CON group, the mice in the AP group exhibited significant edema, inflammatory cell infiltration, necrosis of pancreatic tissues, as well as elevated levels of serum amylase, lipase, and pancreatic myeloperoxidase activity (P<0.05); in comparison to the AP group, inflammatory cell infiltration and necrosis of pancreatic tissue, as well as elevated level of serum amylase significantly reduced in the APQ group (P<0.05). A total of 319 lipid molecules were identified in serum, and 13 lipid metabolites were significantly increased in the AP group and successfully decreased in the APQ group, of which 9 were lyso-phosphatidylethanolamine (LPE) molecules involved in the glycerol phospholipid metabolic pathway. Further statistical analysis revealed that six of these LPE molecules could serve as potential biomarkers. Conclusions CQCQD ameliorated pancreatic injury and serum lipid metabolism disorder of acute pancreatitis model induced by cerulein and significantly improved the abnormal increase of serum LPE level. However, the role of LPE in acute pancreatitis and the underlying mechanisms of CQCQD on LPE metabolic pathways still need further study.