Objective To study the protective effect of heme oxygenase-1 (HO-1) overexpression in extending cold preservation time of liver.Method Isolated perfused rat liver model was set up and rats were given cobalt-protoporphyrin (CoPP) as an HO-1 inducer and zinc protoporphyrin (ZnPP) as an HO-1 inhibitor. Livers were preserved for 0 h, 6 h, 24 h respectively and perfused for 2 h in vitro. Bile production, levels of AST, LDH, TNF-α and IL-6, tissue MDA concentration, HO-1 expression and apoptosis were determined.Results CoPP induced HO-1 overexpression. The levels of AST, LDH, TNF-α, IL-6, tissue MDA, apoptotic cells were decreased and the bile production in CoPP treatment group was increased as compared with the 24 h preservation group without CoPP treatment (P0.05). No significant difference was found between the results of 6 h preservation group and those of CoPP treatment group. These protective effects were abolished by the administration of ZnPP.Conclusion Overexpression of HO-1 extends the cold preservation time of liver from 6 h to 24 h. The mechanisms underlying these beneficial effects include reduced oxidative injury and inflammatory response and prevention of apoptosis.