Abstract: Animals fed Catha edulis leaves develop an acute hepatitis and long-term feeding is associated with chronic active hepatitis and fibrotic liver disease. Repeated episodes of subclinical hepatitis with evolution to chronic liver disease has also been observed in patients chewing Catha edulis leaves. The aim of this study was to examine the effect of 10% Catha edulis on enzyme markers of carcinogenicity in relation to chemically-induced hepatocellular carcinoma in rabbits. Forty healthy male white New Zealand rabbits were allocated to one of five groups (eight rabbits per group). Two control groups fed on control diet with or without sodium nitrite+diethylamine, two treatment groups fed on a diet containing 10% Catha edulis with or without sodium nitrite in water and a fiveth group fed on diet containing tannin. Fasting blood samples were collected at different time intervals (1, 8 and 20 weeks) and plasma was assayed for γ-glutamyl transpeptidase, β-glucuronidase, LDH, AST and ALT using enzymatic kits. 10% Catha edulis alone did not affect these enzymes, however, animals maintained on 10% Catha edulis and sodium nitrite (4000 ppm) (58.82 mM) significantly increased the activities of γ-glutamyl transpeptidase, β-glucuronidase and LDH in a similar manner to those animals exposed to both carcinogens (nitrosamine precursors and commercial tannin). This raises the question of whether the Catha edulis hepatoxicity could be attributed to possible formation of nitrosamines in vivo from the secondary amines present in Catha edulis leaves; as well as highlighting the significance of these enzyme markers in early detection of chemically-induced HCC.