Objectives: New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Racl-Guanosine triphosphate (Racl-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model. Methods: Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time polymerase chain reaction and Western blotting, respectively. Results: Curcumin treatment of BDL rats reduced liver injury, as verified by improvement of hepatic cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the increase in the expression of Racl, Racl-GTP, and NOX1 observed in BDL rats was precluded and reversed back toward normalcy by curcumin treatment (P < 0.05). We also observed an escalation of protein thiol groups, increased enzyme activity of serum antioxidant markers (e.g., superoxide dismutase) and a decrease of carbonylation in curcumin-treated BDL rats compared with BDL rats (P < 0.05). Conclusions: Curcumin attenuated liver damage through the downregulation of Racl, Racl-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver tissue of BDL rats. (C) 2016 Elsevier Inc. All rights reserved.