<b>Background and Objective:</b> The liver plays an important role in transforming and clearing chemicals in human body. Hepatic injury is usually caused by numerous toxic chemicals such as carbon tetrachloride, thioacetamide, galactosamine and drugs including paracetamol as overdoses consumption. This investigation aimed to study the immunomodulatory protective effects of black seed (<i>Nigella sativa</i> L.) oil and lettuce (<i>Lactuca sativa</i> L.) oil against paracetamol liver intoxication in rats. <b>Materials and Methods:</b> Twenty-four male albino rats weighing 150±10 g each, were randomly divided into 4 equal groups (6 rats each) as follows: Control negative; control positive as paracetamol hepatotoxicity; <i>Nigella sativa</i> oil and <i>Lactuca sativa</i> oil at a dose of 1 mL kg<sup>1</sup> b.wt., as protective from hepatotoxicity, then serum analysis for all rats were conducted and the obtained data were analyzed using SPSS version-22. <b>Results:</b> All rats orally preventable injected with <i>Nigella sativa</i> and <i>Lactuca sativa</i> oils caused significant decrease in Unsaturated Iron Binding Capacity (UIBC), creatine kinase (CK), Creatine Kinase-MB (CKMB), magnesium (Mg), phosphor (Phos.), iron (Fe), sodium (Na), potassium (K), amylase (Amyl), tri-glycerides (TG), total cholesterol (TC), Low Density Lipoprotein (LDL), creatinine (Creat), Lactate Dehydrogenase (LDH) as compared to liver intoxicated rats. <b>Conclusion:</b> Black seed oils and <i>Lactuca sativa</i> oils could be used as natural immunomodulatory agents against paracetamol liver intoxication and enhance the body's immune functions with improving the health status of the liver.
Keywords: Hepatotoxicity; black seed; immunomodulatory; lettuce; rats.