Background: The cephalosporins are β-lactam antibiotics that, in terms of both structure and function, are very similar to penicillin. Cefepime is one of the most widely used parenteral fourth generation cephalosporins with broad-spectrum action. The administration of a high dose of cefepime can exert a direct cytotoxic effect which accumulated in the tubular epithelial cells. Objective: The present work aimed to reveal the histological and ultrastructural alterations in the kidney of the adult albino rats in relation to the dose of cefepime given. That's may give a new insight into the prophylaxis of cefepime nephrotoxicity. Material and methods: 25 adult albino rats were divided into five equal groups. In group I (control group) each rat was injected intramuscularly with 1 ml isotonic saline solution /day for one week. Each rat of group II, III, IV and V was injected by cefepime intramuscularly in doses 50, 75, 100 and 125 mg/kg/day respectively for one week. After 2 months kidneys of rats were excised for routine histological and electron microscopic studies. Results: Intramuscular injection of cefepime led to histological and ultrastructural alterations of the cortex and medulla which were marked with increasing its concentration. Cytotoxic damage to the renal tubules, glomeruli and interstitium was obtained. The histological and ultrastructural changes in the kidney caused by cefepime were marked in group III, IV and V. Conclusion: Cefepime nephrotoxicity were marked with increasing its concentration which proves that, cefepime nephrotoxicity in rats were dose related.