Abstract : Ecstasy 3, 4-Methylenedioxymethamphetamine or MDMA is a psychostimulant drug capable of inducing psychiatric disorders in animals and humans. MDMA produces short-term pleasure effects but prompts to neuropsychiatric problems in the long-term, such as anxiety. The purpose of this study was to examine the anxiolytic potential of a natural compound known as thymoquinone (TQ) in rats that were stimulated to anxiety by MDMA. The administration of TQ into MDMA-induced 5-HT depletion rats was carried out in male Sprague Dawley via 1-week treatment dividing into four groups. The administration of TQ into MDMA-induced 5-HT depletion rats was carried out in male Sprague Dawley via a1-week treatment dividing into four groups. The studied groups involved with the treatments comprise i) Control (1 mL/kg saline), ii) MDMA (20 mg/kg MDMA), iii) MDMA-TQ (20 mg/kg MDMA + 40 mg/kg TQ) and iv) TQ (40 mg/kg TQ). Anxiety test is subject to a light-dark test and social interaction test. Our results demonstrated an increase in anxiety behaviour in the MDMA group as compared to the control group. TQ prevented anxiety after undergoing a 1-week treatment in the MDMA+TQ group as compared to the untreated MDMA group. Hence, this study proposed that TQ could protect against anxiety-like behaviour upon MDMA exposure in rats.