AIM: To study the effect of bilirubin on the oxidative liver status and the activity and expression of heme oxygenase-1 (HO-1) in rat liver injury induced by prehepatic portal hypertension.METHODS: Wistar male rats, weighing 200-250 g, were divided at random into two groups: one group with prehepatic portal hypertension (PH) induced by regulated prehepatic portal vein ligation (PPVL) and the other group corresponded to sham operated rats. Portal pressure, oxidative stress parameters, antioxidant enzymes,HO-1 activity and expression and hepatic sinusoidal vasodilatation were measured.RESULTS: In PPVL rats oxidative stress was evidenced by a marked increase in thiobarbituric acid reactive substances (TBARS) content and a decrease in reduced glutathione (GSH) levels. The activities of liver antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also diminished while activity and expression of HO-1 were enhanced. Administration of bilirubin (5 μmol/kg body weight) 24 h before the end of the experiment entirely prevented ali these effects. Pretreatment with Sn-protoporphyrin Ⅸ (Sn-PPIX) (100 μg/kg body weight, i.p.),a potent inhibitor of HO, completely abolished the oxidative stress and provoked a slight decrease in liver GSH levels as well as an increase in lipid peroxidation. Besides,carbon monoxide, another heme catabolic product, induced a significant increase in sinusoidal hepatic areas in PPVL group. Pretreatment of PPVL rats with Sn-PPIX totally prevented this effect.CONCLUSION: These results suggest a beneficial role of HO-1 overexpression in prehepatic portal hypertensive rats.