We investigated the protective role of aminoguanidine (AG) in rat liver injury induced by chronic biliary obstruction. Secondary biliary cirrhosis was induced by bile duct ligation for 14 days. Swiss albino rats were divided into three groups: Common bile duct ligated (CBDL) rats; Group A, CBDL rats treated with AG as Group B and simple laparotomy group known as the Sham group; Group C. Group B received 200 mg/kg of AG intraperitoneally daily throughout 14 days. The present data showed decreased gama glutamyl transferase (GGT), aspartate aminotransferase (AST), bilirubin and alanine aminotransferase (ALT) levels in the AG treated rats, when compared with CBDL rats (p < 0.05). In the AG treated rats, tissue levels of malondialdehyde (MDA) were significantly lower than that in CBDL rats (p < 0.001). Although the levels of glutathione (GSH) in AG treated rats were higher and myeloperoxidase (MPO) were lower than that in CBDL rats, the difference was not statistically significant(p > 0.05). The levels of interieukin-l alpha\ (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha) were significantly lower and although the levels of interleukin-6 (IL-6) were lower in AG treated rats than that in CBDL rats, the difference was not statistically significant. Administration of AG in the rats with biliary obstruction resulted in inhibition of ductular proliferation and portal inflammation. The present study demonstrates that intraperitoneal administration of AG in CBDL rats maintains antioxidant defenses, reduces liver oxidative and cytokine damage and ductular proliferation and portal inflammation. This effect of AG may be useful in the preservation of liver injury in cholestasis. Copyright (C) 2006 John Wiley & Sons, Ltd.