AIM:To study the role of free fatty acids (arachidonic acid and linoleic acid) in proliferation of rat hepatic stellate cells (HSC).METHODS:HSC were isolated and cultured from liver of Wistar rats by in situ perfusion with pronase and collagenase, and density gradient centrifugation with Nycodenz.MTT colorimetric assay was detected for HSC proliferation.RESULTS:Arachidonic acid and linoleic acid had an effect on proliferation of HSC. 25mg/L of arachidonic acid promoted HSC proliferation (P < 0.01), but 50 and 100mg/L had an inhibitory effect on HSC (P < 0.01),and showed cytotoxity on HSC under inverted microscope; 6.25, 12.5, 25ug/ml of linoleic acid had no effect on HSC proliferation (P > 0.05), but with concentration increasing, 50 and 100mg/L of linoleic acid might promote HSC proliferation (P < 0.05 or 0.01 ).CONCLUSION:Arachidonic acid and linoleic acid may promote HSC proliferation, but increased concentration can have cytotoxity on HSC. Arachidonic acid and linoleic acid might be associated with fatty liver and hepatic fibrogenesis by lipid peroxidation.