Objective: The aim of the present study was to investigate the hepatotoxic effect and biochemical alterations induced by ceftriaxone in rats. Methods: Rats were injected ceftriaxone intramuscularly with 180 (therapeutic dose) and 360 (doupletherapeutic dose) mg/kg b.wt. daily for five consecutive days. Blood and liver samples were collected for quantitative determination of some biochemical parameters and histopathological examination respectively. Results: Ceftriaxone produced significant increase in serum concentrations of liver enzymes (AST and ALT), total bilirubin, cholesterol, Tg and LDL-cholesterol. Ceftriaxone also caused significant decrease in albumin and HDL-cholesterol. Ceftriaxone injection in the tested doses caused histopathological changes in liver. The severity of these changes was dose dependant. Conclusion: Hepatic functions should be monitored and/or the dose should be adjusted during ceftriaxone therapy. Key words: Ceftriaxone, Biochemical, Histopathology, Hepatotoxicity, Rats.