High rate of dependence on medicinal plants for maintenance of health care needs over the decades in communities all over the world especially in Africa and Asia needs adequate scientific verification and authentication. Liver related diseases have however become a global problem. Jaundice was established on 9 of a total population of 12 rabbits of mixed sex, weighing 1.50kg - 2.34kg using an overdose pretreatment of Rifampicin (300mg/ kg bw) P.O. After 3 days, the Animals were administered with various doses of aqueous extract of Azadirachta indica (600, 750, 900mg/kg bw) P.O for each group of rats – A, B, C and D (control ), after which the animals were bled via marginal ear vein at zero hour, 7th and 14th days and the blood used for the following assays: Alkaline Phosphatase, Acid Phosphatase, Total Bilirubin, Conjugated Bilirubin and Alanine Transaminase. Experimental animals exhibited lack of appetite, reduced activity, scratching of the body, emesis, yellow coloration of the sclera, light-colored stool and a little dark urine over time. There was also increase in the levels of the biochemical parameters as the day increased. Aqueous extract of Azadirachta indica (Neem) exhibited increasing elevated levels of Alkaline Phosphatase (ALP), Acid Phosphatase (AP), Total Bilirubin (T/Bil), Conjugated Bilirubin (Conj/Bil), and slightly in Alanine Transaminase (ALT), thus exerted elevated hepatotoxicity on Rifampicin-induced Rabbits. Therefore, the traditional use of Azadirachta indica in management of jaundice should be discontinued.