Background and Aims: Long term glucocorticoid treatment stimulates the differentiation of pre-adipocytes to adipocytes, regulated by Iip-hydroxysteroid dehydrogenase type 1 (llp-HSDl) enzyme. lip-HSDl catalyzes the activation of cortisol from its inactive form and amplifies glucocorticoid-mediated adipocyte differentiation, thus, leads to obesity. Palm tocotrienol extract (gamma tocotrienol) was shown to decrease the body fat mass of adrenalectomized rats treated with dexamethasone. This study was conducted to evaluate effects of palm tocotrienol on expression and activity of Iip-HSDl enzyme and fat deposition in the liver of adrenalectomized rats receiving long term glucocorticoid treatment. Methods: Thirty eight male Sprague-Dawley rats were randomly divided into five groups: Baseline group, B (n = 6), Sham group, SS (n = 8) and three adrenalectomized groups (n = 24). Baseline group rats were sacrificed after two weeks of acclimatization. Adrenalectomized groups were given intramuscular Dexamethasone and subdivided into study control group, SC (n = 8), Glycyrrhizic acid treated group, SG (n = 8) and Palm tocotrienol treated group, SP (n = 8). Sham group rats were given intramuscular and oral gavage palm olein as vehicle. Results: Following eight weeks of treatment, the rats supplemented with Palm tocotrienol showed significant reduction in the expression of lip-HSDl enzyme in the livers. The activities of lip-HSDl enzyme in this group were reduced with no significant difference. There was no fat deposition seen in the liver architecture. Conclusion: Palm tocotrienol has the potential to inhibit lip-HSDl enzyme and subsequently prevents the glucocorticoid excess, therefore lowering the risk of obesity in patient receiving long term glucocorticoid treatment.