Nephrotoxic effect and biochemical alterations induced by ceftriaxone were investigated in rats following repeated intramuscular injections of 180 and 360 mg/kg b.wt. daily for five consecutive days. Cefetriaxone is a beta lactam third generation cephalosporin antibiotic of broad spectrum antibacterial activity, targeted for treatment of bacterial diseases. Some serum and urine biochemical parameters and histopathological changes of the kidneys were measured in rats during and after intramuscular injection of cefetriaxone. Significant increase in the total amount of urine per day, urea and creatinine concentration in serum and urine and significant decrease in their clearance. Ceftriaxone also caused significant gluocosuria and proteinuria and significant decrease in their serum concentrations. The effect of ceftriaxone on some electrolytes were also determined. Ceftriaxone injection in the tested doses caused histopathological changes in kidney. The severity of these changes was dose dependant. In conclusion, the renal functions should be monitored and/or the dose should be adjusted during ceftriaxone therapy.