SummaryThe purpose of this study was to investigate the effects of thymoquinone (TQ) on plasma hormone levels, which regulate energy metabolism, and on the lipid profile of rats fed a standard and fatty diets. The study was performed on four experimental groups for 6 weeks using Wistar Albino rats weighing 200-260 g, aged 5-6 months, with 10 rats in each group. 1) The control group: Rats were fed a standard diet and given 1 ml 0.9% saline /kg body weight/day by gastric gavage.2) The TQ group: Rats were fed a standard diet and given 50 mg TQ/kg body weight/day dissolved in 1 ml 0.9% saline, by gastric gavage.3) The fatty diet (FD) group: Rats were fed an experimental diet containing 50% animal fat and given 1 ml 0.9% saline/kg body weight/day by gastric gavage. 4) The FD+TQ group: Rats were fed an experimental diet containing 50% animal fat and given 50 mg TQ/kg body weight/day dissolved in 1 ml 0.9% saline by gastric gavage. At the end of the experimental period, plasma insulin, thyroxine (T 4 ), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were significantly decreased in the TQ group compared with the control group while the plasma glucose level was increased (P<0.01). In the FD group compared to the control group, HDL and carnitine levels were significantly decreased while plasma leptin, glucose, total triiodothyronine (T 3 ), T 4 , free triiodothyronine (FT 3 ), free thyroxine (FT 4 ), trigliseride (TG), LDL and very low-density lipoprotein (VLDL) levels were significantly increased. Compared to the FD group, in particular, leptin, T 3 , FT 4 , TG, LDL and VLDL levels were significantly decreased in the FD+TQ group except for increased glucose. The study concludes that TQ may be a natural source for the provention of the harmful effects of a fatty diet, due to the dropped levels of leptin, TG, LDL, VLDL and could be considered for use in the field of preventive medicine.