Introduction: Tramadol hydrochloride is a synthetic opioid. It is a centrally acting analgesic drug widely used in the treatment of pain. Curcumin is a medicinal plant extensively used as a home remedy for various diseases. It is shown to have anti-inflammatory and antioxidant properties. Aim of the work: The aim of the study was to detect the toxic effects of the tramadol on the histological structure of the liver tissue and to study the possible protective role of curcumin against its toxic effects. Materials and Methods: 30 adult albino rats were used .The animals were divided into three groups each of them consists of 10 rats: Group I: (control group): Animals were given normal saline orally by intragastric tube in a dose of 25ml/kg every day for one month. Group (II): Animals were given Tramadol Hydrochloride in a dose of 25mg/kg body weight orally by intragastric tube every day for one month. Group (III): Animals were given Tramadol Hydrochloride in a dose of 25mg/kg body weight and Curcumin solution in a dose of 80mg/kg body weight orally by intragastric tube every day for one month. At the end of the experiment, the rats were anaesthetized by ether then perfused with saline then with the appropriate fixator, the liver was obtained and subjected to light and transmission electron microscopic studies. Results: tramadol caused dilatation in the central vein, blood sinusoids and degeneration of hepatocytes at light and electron microscopic examination and statistical studies. Administration of curcumin could improve these effects. Conclusion: tramadol caused loss of normal pattern of hepatic tissue with degeneration of some hepatocytes. Curcumin improved the picture of the liver tissue and decreased degeneration in hepatocytes.