All rights reserved. cookware (NRC, 2006) and in topical agents (toothpastes, dental varnishes, gels, rinses, tablets, and drops) designed to reduce dental decay. As a result, the consumption of fluoride became uncontrolled and unpredictable often exceeding its therapeutic window, particularly among children (Natalia and Gennadii, 2012). An excessive fluoride consumption has been linked to development of fluorosis, a slow degenerative diseases, affecting teeth and bone tissues (Sarkar et al., 2014), as well as inducing neurological defects (Malin and Christine, 2015). During recent decades, numerous investigations have established the toxicity of fluoride Abstract Background: Fluoride is widely distributed in nature in many forms and its compounds are being used extensively. Increased oxidative stress is proposed to mediate the toxic effects of fluoride on soft tissues. Thymoquinone (TQ), the major bioactive ingredient isolated from Nigella sativa seed, has been studied for its anti-oxidant properties. Accordingly, this work was conducted to investigate the possible protective effects of TQ against sodium fluoride (NaF)-induced hematological and biochemical toxicity in male albino rats Method: Seventy animals were divided into 7 equal groups. Group I served as negative control group. Group II or positive control group received distilled water orally. Group III received TQ orally at a dose of 10 mg/kg for 5 weeks. Group IV and group V were intoxicated with NaF orally in two different doses: 10 mg/kg and 20 mg/kg respectively for 4 weeks. Group VI was given 10 mg/kg TQ one week prior administration of both TQ and Na F at a dose of 10mg/kg for 4 weeks. Similarly group VII received 10 mg/kg TQ for one week then concomitantly with Na F at a dose of 20 mg/kg for 4 weeks. At the end of the experiment, the animals were sacrificed and blood samples were obtained for assessment of hemoglobin (Hb) concentration, red cell count (RBC), total leucocytic count (TLC), platelet count, serum cholesterol, triglycerides (TG) and blood glucose level in addition to liver enzymes, total bilirubin level and total serum proteins. Oxidative indices including antioxidant enzyme superoxide dismutase (SOD), total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) were also assessed. Results: NaF intoxicated groups showed significant alterations of hematological and biochemical indices with significantly depleted SOD, decreased TAC and concomitant increase in TBARS and AOPP. Pretreatment by TQ mitigated both hematological and biochemical changes induced by NaF probably due to its strong antioxidant activity. Conclusions: The results obtained indicate the role of oxidative stress in NaF toxicity and suggest a possible protective effect of TQ against the toxicity of fluoride compounds.