Coffee is the most frequently consumed beverage worldwide that affects several body organs and systems. This work was designed to evaluate the possible modulating effects of caffeine on hepatotoxicity induced by acute paracetamol (PCM) intoxication in rats.  Ninty adult male albino rats were classified into 4 main groups: Group 1 (negative control) contains 10 rats, Group 2 (positive control) contains 40 rats which is divided equally into 4 subgroups: [2a] received distilled water,  [2b] receiving 30 mg/kg caffeine, (2c) receiving 100 mg/kg caffeine, [2d] receiving PCM 2 g/kg, Group 3 contains 20 rats which is divided equally into 2 subgroups: [3a] Rats were treated on the 14th day only with caffeine 30 mg/kg plus 2 g/kg PCM, [3b]:  Rats were  treated on the 14th day only with caffeine 100 mg/kg plus 2 g/kg. PCM, Group 4  contains 20 rats which is divided equally into 2 subgroups: [4a]: Rats were treated daily with 30 mg/kg caffeine then on the 14th day rats were given  also 2 g/kg PCM and [4b]: Rats were treated daily with 100 mg/kg caffeine then on the 14th day rats were given also 2 g/kg PCM. Blood samples were obtained for estimation of liver enzymes then rats were sacrificed and samples of liver tissue were used for measurements of oxidative stress markers malondialdehyde and advanced oxidation protein products and antioxidants superoxide dismutase and catalase also, the remaining tissue was subjected to histopathological and immunohistochemical localization of Bcl2. Paracetamol induced acute hepatotoxicity which were evident biochemically and confirmed by histopathology (massive necrosis, hemorrhage and inflammation), and immunohistochemistry (marked expression of Bcl2 indicating severe necrosis). The use of single dose 30 mg/ kg of caffeine did not improve the liver, but repeated caffeine 30 mg/kg, partially opposed the toxic effect of PCM through some improvement in all previous parameters. However, increasing the dose of caffeine to 100 mg/kg either in a single dose or in repeated doses enhanced the ability of caffeine to provide nearly complete improvement of hepatotoxicity. Caffeine can modulate hepatic damage induced by acute PCM intoxication.