Abstract: Objective　To investigate the effect of irbesartan on steatosis in LO2 cells by regulating PPAR-γ-mediated AMPK/mTOR signaling pathway and autophagy. Methods　The cell model was established by lipid mixture (LM). LO2 model cells were divided into model group, irbesartan group and irbesartan + PPAR-γ antagonist group. The normal cells were served as the normal group. After 24 hours of intervention, the triacylglycerol (TG) and total cholesterol (TC) levels in cells were measured using enzyme-linked immunosorbent assay (ELISA) kits, and cultured cells were stained with oil red O solution to assess the lipid content. The expression levels of PPAR-γ and AMPK/mTOR signaling pathway molecules in cells were detected by Western blot assay, and the changes of autophagy marker protein LC3B were observed by confocal microscopy and Western blot assay. The changes of autophagy marker protein LC3B were observed by laser confocal technique. Results　The concentration of irbesartan in 10μmol/L and below had no obvious toxic effect on the growth of LO2 cells, but 20 μmol/L irbesartan had a significant inhibitory effect on cell viability. Compared with the normal group, the intracellular TG and TC levels as well as lipid deposition were significantly increased in model group, the expressions of PPAR-γ, P-AMPK and LC3B proteins were decreased, and the level of phosphorylated mTOR was increased (P＜0.05). Compared with the model group, the intracellular TG and TC levels as well as lipid deposition were significantly decreased in irbesartan group. Moreover, it was found that irbesartan strongly increased the expressions of PPAR-γ, p-AMPK and LC3B, and reduced the level of phosphorylated mTOR in LM-induced LO2 cells (P＜0.05). However, these effects were reversed by irbesartan and PPAR-γ inhibitor treatment. It was found that irbesartan strongly increased the expressions of PPAR-γ, p-AMPK and LC3B, and reduced the level of phosphorylated mTOR in LM-induced LO2 cells (P＜0.05). Conclusion　Irbesartan alleviates lipid deposition and hepatic steatosis by activating PPAR-γ mediated AMPK/mTOR signaling pathway, thereby inducing hepatocyte autophagy.