Objective To construct a stable model of sustained hepatic hypoperfusion in mice, and to explore the influence of sustained hepatic hypoperfusion on warm ischemic-reperfusion (IR) injury. Methods C7BL/6 mice aged 6-8 weeks old were chosen for model construction. The portal vein of mice was constricted to the syringe needle with diameter of 1 mL. Liver function and histopathology (H-E staining) were tested on 3, 7, 14 and 21 days after constriction. Hepatic warm IR injury of 70% was performed in stable hepatic hypoperfusion models. Liver function and histopathology were tested again at 3, 24 and 48 hours after reperfusion. Wild type C7BL/6 mice were used as controls. Results After portal vein constriction, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rose to different extents, and the levels peaked on day 7 (ALT: [60.8±6.2] U/L vs [25.5±2.8] U/L, P<0.001; AST: [74.9±6.1] U/L vs [39.1±3.2] U/L, P<0.001). Meanwhile, H-E staining showed that the most serious damage to hepatocytes and more inflammatory cell infiltration appeared on day 7 after constriction. On day 21, ALT almost returned to the normal level (P>0.05), but AST was still significantly higher than baseline (P=0.03). Compared with the control group, damage of hepatocytes was more severe in mice with 7 day-hypoperfusion precondition after warm hepatic IR. The transaminase levels peaked at 3 h after reperfusion (ALT: [8 217.0±1 111.8] U/L vs [5 597.4±1 015.3] U/L, P=0.004; AST: [8 548.2±1 155.4] U/L vs [5 765.4±956.9] U/L, P=0.003). At 48 h after reperfusion, ALT and AST were back to the normal levels in the control group, but they kept at higher levels in the hypoperfusion precondition group (ALT: [608.8±442.9] U/L vs [47.4±20.1] U/L, P=0.008; AST: [861.8±442.8] U/L vs [70.8±68.3] U/L, P=0.008). Conclusion A stable mouse model of sustained hepatic hypoperfusion has been successfully constructed. The model has decreased tolerance to warm IR injury in hypoperfusion precondition liver, which can partly mimic the liver graft in donation after cardiac death in clinic.