Objective To investigate the effects of penehyclidine hydrochloride(PHC)precon-ditioning on hepatic ischemia-reperfusion injury (HIRI)in rats.Methods Fifty-four male Sprague-Dawley rats,weighing 230-250 g,were randomly divided into three groups (n =18 each):sham op-eration group (group S),HIRI group (group HR)and penehyclidine hydrochloride group (group PHC).In group S,the hepatoduodenal ligaments of rats were only pulled and separated,then abdo-mens were closed.In group HR,an atraumatic vascular clip was placed on the vessels blocking the portal venous blood supply to the median and left lateral lobes of the liver for 45 minutes,which re-sulted in approximately 70% rat liver ischemia injury.In group PHC,the rats were treated with 0.45 mg/kg penehyclidine hydrochloride at 30 minutes before the portal venous and hepatic arterial were blocked like group HR.Animals were killed at 2 h (T1 ,n =6),4 h (T2 ,n =6),24 h (T3 ,n =6) after HIRI or sham surgery.Liver tissues and blood samples were taken for analysis.The serum con-centration of ALT and AST were measured as the markers of hepatic functional damage.The TNF-a and IL-1βconcentration were measured by the enzyme linked immunosorbent assay (ELISA)tech-nique.The endothelial nitric oxide synthase (eNOS ) and hypoxia-inducible factor (HIF-1α) expression were measured by immunohistochemical staining.Results Compared with group S,the expressions of ALT,AST,TNF-αand IL-1βin groups HR and PHC increased at T1-T3 (P <0.05), which were similar to the change trend of HIR-1αand eNOS expressions (P <0.05).Compared with group HR,the expression of ALT,AST,TNF-αand IL-1βin group PHC decreased at T1-T3 (P <0.05).Nevertheless expression of HIF-1αand eNOS of groups HR and HPC were increased than that of group S,and experssion of HIF-1αand eNOS of group HPC were increased than that of group HR at T1 and T2 (P < 0.05 ).Conclusion PHC preconditioning can protect the liver from HIRI.The mechanism may be associated with the up-regulation of eNOS and HIF-1α,as well as reducing the in-flammatory response.