Antagonism of the glucocorticoid receptor is used to reduce the detrimental effects of elevated glucocorticoid levels and associated metabolic abnormalities. RU486, also referred as mifepristone, is a known antiprogestin that also competitively blocks the glucocorticoid receptor. Pharmacological inhibition of glucocorticoid action using RU486 improves insulin intolerance and obesity. However, the effect of RU486 on lipid metabolism has not been studied. The present study investigates the interaction of RU486 with proteins involved in lipid metabolism through in silico approach using Accelrys Discovery Studio software. We observed that RU486 interacts with the proteins involved in lipogenesis such as hairy enhancer of split -1, fatty acid synthase, liver X receptor β and phosphoenolpyruvate carboxykinase. Also, RU486 binds to phosphodiesterase 3B, a protein engaged in lipolysis. Thus, RU486 exerts a direct effect on lipid metabolism. These results may have implications in the treatment of disorders associated with lipid metabolism.