Objective To evaluate the roles of curcumin in the formation of lipid droplets in the activated HSCs, and further explore the underlying mechanisms. Method Primary hepatic stellate cells (HSCs) were isolated by perfusing the mouse liver with pronase–collagenase followed by density gradient centrifugation. Cells were maintained in DMEM supplemented with 10% of FBS. Unless indicated, semi-confluent HSCs with passage 4-9 were used in experiments. HSCs or AML12 cells were treated with various doses of curcumin for 24h. The changes of lipid droplets were observed under a microscope after oil red staining. The triglyceride (TG) or free fatty acid (FFA) contents were determined by ELISA. The mRNA and protein expression levels of FAS, SREBP-1c, ATGL, and abhd5 were examined by Real-time PCR and Western blotting, respectively. Results In the presence of various dose of Curcumin for 24h, the number of dark red lipid droplets in HSCs positively correlates with the dose of curcumin, indicating a dose-dependent manner of curcumin on intracellular lipid droplets levels in HSCs. Those phenomena were not detected in the negative control cells, AML12. Compared with the control cells without curcumin treatment, the levels of TG and FFA levels in the curcumin-treated HSCs were increased in a dose-dependently manner. In addition, the expression levels of AREBP-1c and FAS (P<0.01)was significantly upregulated, whereas the levels of ATGL and abhd5 (P<0.05) was significantly down-regulated. Conclusion Curcumin can suppress HSCs activation to restore lipid droplets levels in activated hepatic stellate cells by regulating lipid metabolism-related genes.\n\t\t\n\t\tDOI: 10.11855/j.issn.0577-7402.2018.12.05