Abstract Background: The role of cortisol and its increased action/availability is implicated in the
pathogenesis of insulin resistance associated with obesity and metabolic syndrome but th mechanism of increased action/availability is not known. Availability of several other lipophilic hormones, drugs and pollutants are also reported to be increased in obesity. Increased lipids in the circulation are reported to alter the fluidity and permeability of membranes. Hyperlipidemia is also reported to alter the pharmacokinetics and pharmacodynamics of lipophilic molecules and also membrane fluidity and permeability. In this context we assumed that the hyperlipidemia associate with human obesity might play a role in the altered action/availability of cortisol and this in tur might have initiated the metabolic complications. To evaluate our assumption we hav administered dexamethasone [low [50 μg/kg/day] or high [250 μg/kg/day] dose] to high-fat [coconut oil & vanaspati] fed rats and the results were compared with rats administered with either dexamethasone or high-fat