Arsenic exposure triggers liver fibrosis by disrupting the SIRT1/C/EBPα signaling axis, which normally regulates bile acid detoxification. The study demonstrates that arsenic suppresses SIRT1 expression, increases C/EBPα acetylation, and downregulates key bile acid metabolism genes (Baat, Ugt1a1, Sult2a1, Abcb11). This cascade leads to toxic bile acid accumulation and progressive liver scarring in rats. Resveratrol intervention restored SIRT1 expression, normalized C/EBPα function, and reactivated bile acid detoxification pathways while reducing hepatic arsenic levels. This research illuminates a previously unclear mechanistic link between SIRT1—the longevity-associated deacetylase—and bile acid homeostasis in toxin-induced liver disease. The findings have broader implications beyond arsenic exposure, as bile acid dysregulation underlies various liver conditions including fatty liver disease and cirrhosis. While resveratrol's hepatoprotective effects align with previous research, the specific SIRT1-bile acid axis represents a novel therapeutic target. However, the rat model limits immediate human applicability, and the resveratrol dosing likely exceeds achievable dietary levels. This mechanistic insight advances understanding of how environmental toxins disrupt cellular longevity pathways.