AIM Silent information regulator 1 (Sirtl), a class ⅢI histone deacetylase, has been reported to attenuate myocardial and kidney ischemia-reperfusion(I-R) injury.However, the mechanisms of Sirtl in hepatic I-R have not been elucidated.Carnosic acid (CA), a rosemary phenolic compound, was demonstrated to protect the brain against oxidative stress during middle cerebral artery I-R.The present study was performed to determine CA would reduce hepatic I-R stress and to clarify the molecular mechanisms of CA.METHODS In vivo, rats were randomly exposed to sham-operated group, I-R group (45 rain ischemia to 70% of the liver followed by 90 rain reperfusion), CA (60 mg·kg-1, given 60 rain before surgery), I-R + CA, ischemic preconditioning (IPC).After reperfusion,pathological alterations, apoptosis index, serum aminotransferases and inflammation factors were measured.The expressions of Sirtl,P66shc and NF-κB in hepatic were detected.In vitro, HepG2 cell was treated with CA 2.5, 5 and 10 μmol·L-1.After this treatment,the expression of Sirtl was measured.RESULTS In vivo, CA and IPC decreased I-R-mediated the sermn levels of aminotransferases,inflammatory response and hepatocellular damage.Hepatic I-R injury was associated with decreased Sial, increased P66ahc and upregulated NF-κB, which were prevented by CA and IPC.CA and IPC also significantly attenuated levels of I-R-induced hepatic cell apoptosis.In vitro, CA increased the Sirtl protein level in a dose and time-dependent manner.CONCLUSION For the first time, we confirm that CA can protect hepatic against inflammation and apeptosis caused by I-R through Sirtl pathway.These results reveal a new protective mechanism elicited by CA-induced SIRT1 activation in I-R tissues and suggest a novel potential therapeutic targets to manage 1-R-induced hepatic dysfunction.