This study investigates the mechanism by which Salvianolic acid B (Sal B) attenuates liver fibrosis by targeting extracellular matrix protein 1 (Ecm1) and inhibiting hepatocyte ferroptosis. Sal B, a natural antioxidant, has been shown to have antifibrotic effects, but its specific mechanism remains unclear. The researchers induced liver fibrosis in wild-type and Ecm1-deficient mice using carbon tetrachloride (CCl4) and treated them with Sal B, ferrostatin-1, sorafenib, or cilengitide. They found that Sal B significantly reduced liver fibrosis in CCl4-induced mice, and this effect was abolished in Ecm1-deficient hepatocytes. Mechanistically, Sal B protected hepatocytes from ferroptosis by upregulating Ecm1. Further studies revealed that Ecm1 interacts with xCT to regulate hepatocyte ferroptosis. In vitro, Sal B treatment reduced hepatocyte ferroptosis, which was abrogated by Ecm1 knockdown in LO2 cells. These findings suggest that Sal B alleviates liver fibrosis by upregulating Ecm1 and inhibiting hepatocyte ferroptosis, with Ecm1 interacting with xCT to regulate this process.This study investigates the mechanism by which Salvianolic acid B (Sal B) attenuates liver fibrosis by targeting extracellular matrix protein 1 (Ecm1) and inhibiting hepatocyte ferroptosis. Sal B, a natural antioxidant, has been shown to have antifibrotic effects, but its specific mechanism remains unclear. The researchers induced liver fibrosis in wild-type and Ecm1-deficient mice using carbon tetrachloride (CCl4) and treated them with Sal B, ferrostatin-1, sorafenib, or cilengitide. They found that Sal B significantly reduced liver fibrosis in CCl4-induced mice, and this effect was abolished in Ecm1-deficient hepatocytes. Mechanistically, Sal B protected hepatocytes from ferroptosis by upregulating Ecm1. Further studies revealed that Ecm1 interacts with xCT to regulate hepatocyte ferroptosis. In vitro, Sal B treatment reduced hepatocyte ferroptosis, which was abrogated by Ecm1 knockdown in LO2 cells. These findings suggest that Sal B alleviates liver fibrosis by upregulating Ecm1 and inhibiting hepatocyte ferroptosis, with Ecm1 interacting with xCT to regulate this process.