Introduction: Although acetaminophen is a widely used analgesic antipyretic, its toxicity is one of the most common causes of acute liver failure worldwide. N-acetyl cysteine (NAC) is the standard antidote for acute acetaminophen toxicity. Both coenzyme Q10 (CoQ10) and Aloe vera have antioxidant and anti-inflammatory effects so they are used in wide varieties of medical applications Objective: The aim of this work was to compare the possible hepatoprotective effects of NAC, CoQ10 and Aloe vera gel in acute acetaminophen induced hepatotoxicity in albino rats. Materials &Methods: Sixty male albino rats were divided into 3 groups, group I (control group) was further subdivided into 4 equal subgroups Ia, Ib, Ic and Id (n=5) receiving tap water, NAC (450mg/kg) as a single oral dose, CoQ1010mg/kg as a single i.p injection, Aloe vera (500mg/kg) as a single oral dose respectively. GroupII (n=10) received acetaminophen (700mg/kg) as a single oral dose. Group III was further subdivided into 3 subgroups IIIa, IIIb and IIIc (n=10), each received the same dose of acetaminophen as group II followed 1 hour later by NAC, CoQ10 or Aloe vera gel respectively in the same doses as group I. After 24 hours the rats were sacrificed under anesthesia and blood samples were collected for estimation of serum aspartate transaminase (AST) (Aspartate transaminase AST) and alanine transaminase (ALT) (Alanine transaminase ALT) levels. Liver homogenates were used for estimation of malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH). Liver specimens were harvested from all rats at the end of the experiment for histological examination by the light and electron microscopes. Results: Acetaminophen induced hepatotoxicity, as it significantly elevated AST, ALT and MDA and depleted liver GSH and SOD. NAC, CO Q10 and Aloe vera gel had hepatoprotective effects as they reversed these effects. Histologically, group Ib, Ic and Id revealed almost the control pattern of liver similar to group Ia. Group II liver sections showed loss of normal hepatocellular architecture with cellular infiltration and dilated congested blood vessels. Most of the hepatocytes appeared swollen with cytoplasmic vacuolation. Dark shrunken nuclei were encountered. Ultrastructurally, dense mitochondria, dilated profiles of rER and numerous lipid droplets were revealed. Many apoptotic bodies were further encountered. Both group IIIa and IIIc revealed almost the control pattern of the liver except for few areas of cellular infiltration and vascular dilatation and congestion in group IIIa. Group IIIb showed considerable improvement with persistent focal areas of hepatic affection. Conclusion: This study showed that NAC, CoQ10 and Aloe vera have significant hepatoprotective effects in acetaminophen induced hepatotoxicity, best seen with NAC and Aloe vera gel and less with CoQ10. Recommendations: Further study is recommended to explore the possible hepatoprotective effects of coenzyme Q10 and Aloe vera in chronic acetaminophen as well as other toxins induced he...