Liver dual arterial blood supply (LDABS) could increase blood supply to the liver and maintain normal liver regeneration in patients with compromised portal vein. The current study attempted to examine the underlying molecular mechanisms. Male Sprague-Dawley rats randomly received partial hepatectomy (PH) alone or PH followed by LDABS. Liver regeneration was assessed by histological examination, liver function and liver regeneration rate (LRR). Whole-genome oligo microarray analysis was used to compare gene expression profile between rats receiving PH and rats receiving PH plus LDABS. Key genes identification was validated using a MAPK signaling polymerase chain reaction (PCR) array. The extent of liver regeneration in rats receiving PH plus LDABS was comparable to that in rats receiving PH alone. The differentially expressed genes were enriched in 12 signaling pathways in two groups. MAPK signaling pathway, NF-kappa B signaling pathway, and Toll-like receptor signaling pathway were involved in LDABS-mediated liver regeneration, with Retinoblastoma 1 (Rb1), Cyclin D1, Cyclin-dependent kinase 4, Mitogen-activated protein kinase 10 (Mapk10) and CAMP responsive element binding protein 1 genes in the initiation phase, Kirsten rat sarcoma viral oncogene homolog (Kras), tumor protein 53, MYC proto-oncogene, BHLH transcription factor, Cyclin E1 and Heat shock protein family B (small) member 1 genes in the proliferation phase, Kras, Rb1, Jun proto-oncogene, AP-1 transcription factor subunit, Cyclin D2 and Mapk10 genes in the termination phase were identified as key genes in LDABS-mediated liver regeneration using MAPK signaling PCR array analysis.