BACKGROUND፡ Alcohol consumption can cause hepatitis and long-term cirrhosis of the liver. The aim of this study was to evaluate the protective effects of curcumin (CUR) and ursodeoxycholic acid (UDCA) alone and together in the prevention and treatment of liver damage caused by overuse of ethanol.METHODS: Adult Wistar rats were divided into 8 groups of 5, including the control group and various combinations of ethanol, CUR and UDCA groups. Twenty-eight days after the oral treatment, serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and Arginase I (ArgI) as well as serum levels of Albumin (Alb), total protein (TP) and Blood Urea Nitrogen (BUN) were measured, and liver tissue was evaluated histopathologically.RESULTS: The solo administration of CUR, UDCA and CUR+UDCA had no effect on the blood parameters and liver tissue compared to the control group (p˃0.05). The solo administration of CUR and UDCA in ethanol-treated rats significantly reduced ALT, AST, ALP, GGT, ArgI and BUN levels (p˂0.05), while the solo administration increased Alb and TP levels compared to the ethanol group (p˂0.05). In these groups, a significant decrease in cell necrosis and local inflammation of hepatocytes was observed, and the liver damage was mild. However, co-administration of ethanol, CUR and UDCA made significantly greater decrease in ALT, AST, ALP, GGT, ArgI and BUN levels (p˃0.05), while the co-administration greatly increased Alb and TP levels compared to the ethanol group (p˂0.05). Histopathologically, a decrease in structural changes in liver tissue and inflammation was observed, resulting in the improvement of liver tissue.CONCLUSION: The solo administration of CUR and UDCA could reduce ethanol-induced liver damage in rats and improve liver’s serum and blood parameters. However, the co-administration of CUR and UDCA has a greater efficacy.KEYWORDS: Curcumin, Ursodeoxycholic acid, Ethanol, Hepatotoxicity, Rat