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Betamethasone, a fluorinated and synthetic steroid, is a commonly used glucocorticoid. To our knowledge, no available studies exist concerning the hyperlipidemic effect of betamethasone dipropionate (BDP) in rabbits. Therefore, the current study was conducted to highlight the effects of intramuscular injection of BDP on lipid profile in rabbits, investigate the possible mechanism underlying the produced effects and evaluate the possible antihyperlipidemic effect of atorvastatin (ATR) and fenofibrate (FFB). For this purpose, twenty male New Zealand rabbits were classified into control, BDP (0.5 ml/kg B.wt/ IM/day/single dose), BDP+ATR; rabbits were IM injected with BDP, then they were orally given ATR (1.9 mg./kg. B.wt./ once/ day/ month) and group IV (BDP+FFB); rabbits were IM injected with BDP then they were orally given FFB (7.5 mg/kg B.wt/ once/ day/ month). The obtained result revealed that single IM injection of BDP produced a significant elevation in triglycerides, total cholesterol, LDL level with a significant decline in HDL in comparison to control group on the 3rd, 7th, 14th, 21st, 30th day of the experiment. On the 30th day of the experiment there was an increase in the ALT, AST, MDA, VCAM-1 as well as a significant decrease in TAC. Furthermore, BDP induced a significant increase in HMG-COA reductase gene expression and a significant decrease in lipoprotein lipase gene expression. Oral administration of ATR or FFB concurrently with BDP for a month succeeded in reducing the hyperlipidemia induced by BDP in rabbits. [ABSTRACT FROM AUTHOR]