Alcohol-induced liver fibrosis is a great worldwide concern. Rosuvastatin is an anti-hyperlipidemic drug and chrysin is a natural flavonoid. This study examined the potential protective actions of rosuvastatin, chrysin, and their combination against ethanol-induced liver fibrosis based on their anti-inflammatory, antioxidant, and anti-fibrotic effects using silymarin as a reference. Male rats were given ethanol (25%, vol./vol.) (1 ml/100 g/day, P.O.) thrice weekly for seven consecutive weeks. Silymarin (100 mg/kg, P.O.), chrysin (100 mg/kg, P.O.), rosuvastatin (10 mg/kg, P.O.), or a combination of chrysin and rosuvastatin were administrated thrice weekly for seven weeks. Results showed that rosuvastatin and chrysin alone or in combination decreased liver fibrosis initiated by ethanol as hepatic enzymes (ALT, AST, ALP, GGT) were decreased and a decline in 4-HYP; and TGF-β1 levels. This study declared for the first time the hepatoprotective role of rosuvastatin and chrysin combination against liver fibrosis initiated by ethanol via TGF-β1/Smad pathway, decreasing inflammation, oxidative stress, and fibrosis.