Objective: To investigate the alleviation effect of ischemic preconditioning (IP) on hepatic ischemia-reperfusion (I/R) injury in rats and the mechanism. Methods: Fifteen male SD rats were equally randomized into sham operation group, I/R group and IP plus I/R group, respectively. I/R injury model was created by Pringle maneuver (30-min hepatic ischemia followed by 3-h reperfusion), and IP was induced by 10-min hepatic ischemia followed by 10-min reperfusion prior to I/R. Rats in each group were sacrificed and samples were collected after 3-h reperfusion, liver specimen pathological examination and measurement of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were performed, and meanwhile, the NF-κB protein expression, and the levels of inflammatory cytokines (IL-1β and TNF-α) as well as oxidative stress indexes that included malondialdehyde (MDA) and myeloperoxidase (MPO) in the liver tissues were determined. Results: Except in sham operation group, the liver tissues from either I/R group or IP plus I/R group showed pathological changes of liver injury, but the injury was milder in IP plus I/R group than that in I/R group. In both I/R group and IP plus I/R group compared with sham operation group, the serum AST and ALT levels, and liver tissue levels of NF-κB protein expression, IL-1β, TNF-α, MDA and MPO were all significantly increased (all P<0.05), but the increasing amplitudes of all these parameters in IP plus I/R group were significantly less than those in I/R group (all P<0.05). Conclusion: IP lessens hepatic I/R through inhibiting NF-κB activity, and thereby reduces inflammatory and oxidative stress responses.