Aim: Hepatotoxicity, among other adverse effects, constitutes one of the greatest impediments to successful antiretroviral drug therapy (ART) in HIV/AIDS patients. The main objective of the study was to determine if the aqueous leaf extract of Ocimum gratissimum has a protective effect on Original Research Article Ughachukwu et al.; EJMP, 13(1): 1-11, 2016; Article no.EJMP.23603 2 ART-induced hepatotoxicity in rats. Place and Duration: Department of Pharmacology, Chukwuemeka Odumegwu University, Nigeria (six months duration). Methodology: Twenty five (25) albino rats of both sexes were divided into 5 groups of 5 each and treated as follows: Group A (no antiretroviral drugs, no extract); group B (antiretroviral drugs alone); group C (extract alone); group D (antiretroviral drug plus 40 mg/kg extract); group E (antiretroviral drug plus 80 mg/kg extract). All treatment lasted for twenty eight days. Blood samples were collected and serum ALT and AST determined using UV-spectrophotometer. Thereafter, the animals were sacrificed and their livers harvested and examined histologically. The mean (± S.E.M) of data were calculated and further analyzed for statistical significance using graph Pad Prism 5.0. Results: Mean serum ALT were 35.6±6.4, 54.0±9.4, 53.8±22.9, 90.5±21.9, 86.5±13.9 and that of AST were 143.8±19.7, 205.2±14.9, 58.0±27.9, 162.3±41.4, 150.5±44.8 for groups A, B, C, D, and E respectively. There was a statistically significant difference between the mean values of serum AST for group B and those for group C (p value of 0.016). However there was no statistically significant difference between the ALT values for the test and control groups of rats (p value > 0.999). Also, there was no statistically significant difference between the mean values of AST for group B and those of groups A, D, E (p value = 0.659). The histology report for the liver was normal for all groups. Conclusions: This extract did not produce significant reduction of serum ALT and AST in ARTtreated rats in this study.