Liver fibrosis, a critical stage in chronic liver disease progression, presents a significant global health challenge. This study investigates the antifibrotic and hepatoprotective properties of fluorofenidone (AKF-PD) using a 3D tissue-engineered model. A 3D in vitro liver fibrosis model was developed using decellularized rat liver scaffolds seeded with hepatocytes, hepatic stellate cells (HSCs), and sinusoidal endothelial cells to replicate the multicellular liver microenvironment. The model was stimulated with carbon tetrachloride (CCl