Background & Aims Previous studies have demonstrated that 3,5-l-diiodothyronine (T2) is able to prevent lipid accumulation in the liver of rats fed a high-fat diet. Whether this effect is due to a direct action of T2 on the liver has not been elucidated. In this study, we investigated the ability of T2 to reduce the excess lipids in isolated hepatocytes treated with fatty acids (FFAs). The effects of T2 were compared with those elicited by 3,3′,5-l-triiodothyronine (T3).