Objective  To investigate the regulation of liver regeneration (LR) by changes in energy metabolites in the initiation phase during rat liver regeneration.    Methods  Rats were randomly divided into 3 groups with 5 rats in each group, including two partial hepatectomy (PH) groups and one normal control group. Selective reaction monitoring/multiple reaction monitoring (SRM/MRM) was employed in the targeted metabolomics identification of 29 energy metabolites. Ingenuity Pathway Analysis (IPA) was applied for integration analysis, including canonical pathway and molecular interaction network.    Results  The levels of 3-phospho-D-glycerate, AMP, cyclic AMP, D-fructose 1, 6-bisphosphate, dihydroxyacetome phosphate(DHAP), guanosine monophosphate(GMP), guanosine triphosphate(GTP), nicotinamide adenine dinucleotide(NAD) and nicotinamide adenine dinueleotide phosphate(NADP) significantly increased. The levels of alpha-ketoglutarate, beta-D-fructose 6-phosphate, cis-aconitate, D-glucose 6-phosphate, lactate, NADPH, oxaloacetate and pyruvate dramatically reduced. Through hierarchical clustering analysis of energy metabolisms, these energy metabolisms can be grouped into four clusters. IPA showed that the biomolecular changes in the priming phase of liver regeneration are mainly related to carbohydrate metabolism, cellular growth and proliferation, and organismal development. During the priming phase of liver regeneration, adenosine 5’-monphosphate-activated protein kinase (AMPK), hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor (PPAR), protein kinase A (PKA) and phosphatid  linositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways are involved in energy metabolism, and glycolysis may be the main mode of energy supply.    Conclusion  The result  suggests that the changes of energy matabolites during the initial stage of LR play a regulatory role in live regeneration.