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Hydrogen sulfide (H₂S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H₂S could protect livers from ischemia/reperfusion injury (IRI). Male C57BL/6 mice were subjected to partial hepatic IRI for 60 min. Animals received 0 (IRI) or 100 ppm H₂S (IRI + H₂S) from 30 min prior to ischemia until 5 min before reperfusion. Core body temperature was maintained at 37 °C. Animals were sacrificed after 1, 6 or 24 h. Hepatic ischemia caused extensive hepatic necrosis in the IRI animals which coincided with an increase in ALT and AST serum levels. Animals treated with H₂S showed attenuated serum ALT and AST levels and reduced necrotic lesions after 24 h. IRI animals had increased Bcl‐2 mRNA expression and increased active Caspase 3 protein, which were both significantly lower in H₂S treated animals. Increased TNFα and IL‐6 …