ObjectiveTo observe the fatty deposition in thapsigargin-induced endoplasmic reticulum stress model in hepatocytes and to discuss the possible mechanism. MethodsHepatocytes (L02 cell and HepG2 cell line ) were divided into control group and experimental group (treated with 1 μmol/L thapsigargin). Fatty deposition in the hepatocytes was observed by biochemical assay and oil red O staining. Real-time PCR was used to test the expression of SREBP-1c and LXRs mRNA. And Western blotting analysis was used to examine the expression of protein of GRP78,SREBP-1c and LXRs. ResultsWestern blotting analysis showed that GRP78 protein expression in the experimental group was remarkably higher than that in the control group (P<0.05 ), indicating the successful establishment of the endoplasmic reticulum stress model in hepatocytes. The hepatocyte fatty deposition in the experimental group was significantly more than that in the control group 48 h after thapsigargin exposure(P<0.01). The expression of SREBP-1c mRNA and protein in the experimental group was significantly higher than that in the control group (P<0.05 ), and the expression of LXRs mRNA and protein was not significantly between the two groups. ConclusionEndoplasmic reticulum stress may induce hepatocyte fatty deposition throuth up-regulating SREBP-1c, and LXRs is not involved in the process.