Background: Cisplatin (CP) is an alkylating agent with antitumor properties. It has a wide range of adverse effects including hepatotoxicity. Objective: Evaluating the effectiveness of CPon the rat's liver architecture as well as the comparative protective role of vitamin E and Royal Jelly (RJ). Material and Methods: Two sets of forty adult male albino rats with average body weights of 200–250 g each were created at random. Thirty rats were provided as the treated group (group2) divided into three equal subgroups (a, b and c), and ten rats were served as the control group (group1). Ten rats were in subgroup (a), and they received CP treatment. Ten rats from subgroup (b) were administered CP and vitamin E. Ten rats from subgroup (c) were administered CP and RJ. The rat's liver was removed and histologically prepared for evaluation under the light and electron microscopes. Results: Administration of CP to rats produced harmful hepatotoxic effect, these effects relatively improved by administration of vitamin E and RJ, but RJ was observed that had a more potent protective effect on the rat's liver than vitamin E. Conclusion: CP induced hepatotoxicity in animal model while, RJ has a great protective effect against the liver toxicity. Furthermore, vitamin E plays a healing role in the liver damage caused by CP.