Many medicinal plants use traditionally have been in use by man without the actual knowledge of their toxic potential. One of such plants used is tobacco plant leave (Nicotiana tabacum), which is chewed in order to relax the smoker. This work is aimed at determining the biochemical effects of aqueous leaves extracts of Tobacco plant (Nicotiana tabacum) in some liver indices in Wistar albino rats. Four groups of animals were studied. The Wistar rats were divided into four groups. Group 1 was treated with normal saline orally, group 2, 3 and 4 were treated with 0.5mL of the extracts, 200 mg/kg, 400 mg/kg and 600 mg/kg respectively. The animals were by a drop of proparicaine in each eye to minimise discomfort, blood sample was collected through Retro-orbital blood collection method 24 h after the last treatment, then alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities and bilirubin levels were assayed. The result obtained showed a significant (P<0.05) increase in the ALT, AST and ALP activity in the treated group when compared with the control. Also, bilirubin (total and direct) showed a significant (P<0.05) increase in concentration with the total bilirubin having the highest increase in the activity. The present results indicate that the aqueous leaves extracts of Tobacco plant (Nicotiana tabacum) might not be safe for human consumptions as they are associated with liver toxicity.