Aim: To study the comparative effect of Acetaminophen induced liver toxicity with aqueous extract of Azadirachta Indica (Neem) and vitamin E on the basis of liver Histopathology. Methods: Sixty Wistar Rats of both sexes were split into four groups. Each group contained 15 animals. The control group was group A, Group B was treated orally with single dose of Paracetamol 2 mg / kg by weight, Group C was administrated orally with aqueous Neem extract 500 mg/kg +2 mg/Kg by weight oral Paracetamol, and Group D was given orally paracetamol+Neem extract+Vitamin E with 100mg/Kg/body weight for 15 days. Rats from all groups were decapitated, the liver was sliced, and liver tissues were taken for histological examination. Tissue samples were fixed in 10% formaldehyde, embedding in paraffin followed by Hematoxylin and Eosin dye (H&E) and observed under 400x magnification with a digital microscope. Results: On Histopathological examination of the rat`s liver in we found that the control group had a normal appearance, colour, and uniform surface without any necrosis. Group B showed severe necrosis and haemorrhagic patches. In comparison, Group C revealed normal appearance, colour, and smooth surface with no necrotic alterations. Livers from the group D looked virtually normal in terms of colour, undersurfaces, and organ weight. However, hepatoprotective effects were observed in the Group C and D. Therefore, we can conclude that Azadirachta indica and Vitamin E could serve as a good medication for defence against liver injury. Conclusion: Our findings showed thatextract of Azadirachta Indica and Vitamin E exhibited hepatoprotective effects on the Wistar rats that were subjected to Acetaminophen. Key words: Azadirachta Indica leaf extract, Vitamin E, hepatoprotective Paracetamol, Wistar rats.