Background: Liver is a metabolically active organ responsible for many vital life functions. It performsrnmany activities that are critical for survival. Due to its important activities, the liver is exposed to arnnumber of insults and is one of the body's organs most subject to injury. Although antiretroviral drugsrnhave significantly improved morbidity and mortality in HIV-infected patients, these benefits arerncompromised by numerous side effects, adverse clinical events and toxicities. The most common andrntroublesome toxicity of antiretroviral drugs is hepatotoxicity. In spite of tremendous advances in modernrnmedicine, there are hardly any reliable drugs that protect the liver from damage and/or help inrnregeneration of hepatic cell. It is, therefore, necessary to search for effective and safe herbal drugs for therntreatment of liver disease to replace currently used drugs of doubtful efficacy and safety.rnAim of the study: to investigate the hepatoprotective activity of aqueous extract of Nigella sativa seed inrnhighly active antiretroviral therapy (Lamivudine, Zidovudine and Efavirenz) administered rats.rnMaterials and Methods: thirty six rats weighed between 150-200g were randomly divided into sixrngroups and each group comprised of six rats. Rats in group I were administered with distilled water. Ratsrnin group II were administered with highly active antiretroviral therapy only. Rats in groups III - VI werernadministered 100, 200, 400 and 800 mg/kg N. sativa plus highly active antiretroviral therapy respectively.rnThe treatments were given orally for 28 consecutive days. On the 29th day, all rats were sacrificed underrnlight diethyl ether anaesthesia; blood samples were collected for the assessment of biochemicalrnparameters, while liver tissue was used for histopathological assessment.rnResults: Serum levels of liver enzymes ALT, AST, ALP, and GGT were significantly (p