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Solanum nigrum is a medicinal plant commonly known as black night shade and Makoi, it is found in two varieties. One has black colored fruits while the other has reddish brown colored fruit. Traditionally Solanum nigrum possesses a number of active compounds which are responsible for its diverse pharmacological properties. The current study aims to investigate the diethyl ether extract of Solanum nigrum leaves activity on the liver acute toxicity induced by carbon tetrachloride in rabbits. The rabbits were allocated randomly into two groups (n=6). The hepatic damage intensity and protection was observed by biochemically investigating the serum levels of Lactate dehydrogenase (LDH), bilirubin, Alanine transaminase (ALT), Asparate transaminase (AST), alkaline phosphatase (ALP), total protein (TP) and tissue histopathology analysis. The results showed that the diethylether extract of Solanum nigrum leaves have significant (p < 0.05) shielding effect on all hepatic enzymes and protein. Histopathological evaluation also confirmed that diethyl ether extract of leaves has potential to protect the liver against chemical (CCL4) induced injury.