Aims: To determine the median lethal dose (LD50) of crude ethanolic leaf extract of Phyllanthus amarus and evaluate its sub-chronic oral toxicity in experimental mice (BALB/C strain).
 Study Design: One-factor, one-control, one-test group experimental design.
 Place and Duration of Study: Department of Medical Biochemistry, Delta State University, Abraka, Nigeria, between December, 2014 and November, 2015.
 Methodology: Crude ethanolic leaf extract of P. amarus was prepared as previously described and twenty (20) Swiss albino mice (BALB/C strain) were randomly and equally divided into two (2) groups and administered 2000 mg/kg body weight (Group A) and 5000 mg/kg body weight (Group B) of the prepared extract as single oral dose in line with the limit dose method of determining LD50. For the sub-chronic oral toxicity study, ten (10) mice were assigned into control (n=5) and experimental (n=5). The control animals were given placebo-normal saline, but the experimental mice were administered with nocebo – 300 mg/kg body weight of P. amarus crude ethanolic extract for twenty one (21) days. Thereafter, the animals in each group were sacrificed and then, serum and liver homogenate were obtained for the assay of total antioxidant capacity (TAC) and oxidative damage (Malondialdehyde-MDA) Using documented methods. Liver tissue was also processed for histopathological examination using H&E stain.
 Results: Data showed LD50 of the extract to be greater than 5000 mg/kg. Assessment of the herb’s sub-chronic oral toxicity indicates that the leaf extract significantly (P=.03) enhanced total antioxidant capacity (TAC) in both serum (Control: TAC = 0.10±0.03 mM, Experimental: TAC = 0.33±0.05 mM) and liver (Control: TAC = 0.12±0.09 mM, Experimental: TAC = 0.34±0.06 mM) but reduced (P = .01) the biomarker for liver tissue damage (Control: MDA = 41.89±3.36 µM, Experimental: MDA = 4.67±4.04 µM). In addition, hepatic cells were invigorated by P. amarus treatment as suggested by the histopathological features.
 Conclusion: Collectively, P. amarus crude ethanolic leaf extract possesses high degree of tolerance and hepatic tonic potential with no identifiable toxic or side effects.