Cancer is a worldwide growing health problem caused expanding utilization of chemotherapy which is still the most popular and first-line method of treating malignancies. The current study aimed to use histological, histomorphometrical, immunohistochemical, and ultrastructural protocols to evaluate the hepatotoxic effect of Taxol (TXL) and the ameliorative influence of melatonin (MLT) against toxic impacts in the liver of adult rats. Fifty rats were used and randomly divided into four groups: control, sham, TXL (7.5 mg kg¹ i.p.), MLT (10 mg kg^-1 i.p.) and MLT+TXL (10 mg kg^-1 + 7.5 mg kg^-1 i.p.) groups. The results indicated the presence of numerous histopathological, histomorphometrical, and ultrastructural changes in the hepatic tissues of TXL-treated animals including destruction of the normal building of the hepatic lobules, with marked decline in the number of intact hepatocytes, and  a rise in the number of necrotic hepatic cells, centrilobular and periportal inflammatory cells, and degraded Kupffer cells, in addition to  noticeable apoptosis which was represented immunohistochemically by marked elevation in P53 and casapase3 (Cas3), and diminution in Bcl-2 immunoreactivities. Also, strong CD163 immunoreactivity was seen in TXL-treated rats. Nevertheless, co-administration of MLT with TXL reversed most of the histological and ultrastructural alterations triggered by TXL in rats. Moreover, MLT revealed a diminished effect against liver apoptosis and inflammation caused by TXL which was represented by elevation of immunoexpression of Bcl-2 and decreased immunoexpression of P53, Cas3, and CD163. In Conclusion, the present study proved that MLT has ameliorative impact against TXL-triggered hepatic toxicity through its antioxidant, anti-inflammatory and anti-apoptotic properties.