Introduction: Ivermectin (IVM) and paracetamol (APAP) are among drugs used for treatment of mild and moderate cases of covid-19 infection. Aim: this study aimed to evaluate the potential hepatotoxic effects on combination of both Paracetamol and Ivermectin in adult male albino rats. Methodology: fifty adult male albino rats were divided into control groups (negative and Positive) and IVM and APAP treated group which included thirty rats and subdivided equally into 3 subgroups (III A, B, C). Each rat received orally 3.7mg/kg/day of Ivermectin concomitantly with 370 mg/kg /day of paracetamol (groups III A, B, C were sacrificed after 7 days, 14 days and 28 days respectively). Serum levels of aminotransferases ALT, AST, glutamate dehydrogenase (GLDH) and Hyaluronan (HA), Histopathological examination of liver and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Results: HA was elevated after 7 days followed by GLDH which increased after 14 days while aminotransferases levels increase only after 28 days of combined IVM and APAP treatment. After 7 days, the histopathological changes in IVM andAPAP treated group was restricted to congestion of central vein with some vaculation in the hepatocytic cytoplasm then aggravated with increased duration of treatment to periportal fibrosis, inflammatory infiltration areas and necrotic foci. Conclusion: Combination of IVM and APAP induced liver injury, detected 7 days after treatment by HA level and accompanied by histopathological changes which became more severe with increasing duration of treatment. IVM and APAP should be used cautiously to avoid possibility of aggravation of liver injury which is believed to be one of covid-19 complications. Keywords: Ivermectin, Paracetamol, Hepatotoxic, Covid-19, Hyaluronan.