Propofol is an intravenous anesthetic, reported to have a protective effect against ischemia/reperfusion (I/R) injury in heart and brain, but no definite data are available concerning its effect in hepatic I/R. This work investigated the effect of propofol anesthesia on hepatic I/R injury using in vivo rat model. Four groups of rats were included: sham operated, I/R (30 min ischemia and 2 h reperfusion), I/R treated with propofol (10 mg/kg/h), and I/R treated with propofol (20 mg/kg/h). Liver enzyme leakage, TNFand caspase-3 levels, and antiapoptotic Bcl-xL/apoptotic Bax gene expression, together with histopathological changes, were used to evaluate the extent of hepatic I/R injury. Compared with sham-operated group, I/R group showed significant increase in serum levels of liver enzymes (ALT, AST), TNF-, and caspase-3 and significant decrease in the Bcl-xL/Bax ratio, associated with histopathologic damage in liver. Propofol infusion significantly attenuated these changes with reduced hepatic histopathologic lesions compared with nonpreconditioned I/R group. However, no significant differences were found between two groups treated with different doses of propofol. In conclusion, propofol infusion reduced hepatic I/R injury with decreased markers of cellular apoptosis. Therefore, propofol anesthesia may provide a useful hepatic protection during liver surgery.