Paracetamol (acetaminophen-N-acetyl-p-aminophenol, PCM), a most common antipyretic & analgesic compound is widely used for the treatment of cold, cough, fever, pain including chronic pain, muscular ache, migraine, menstrual cramps, headache, backache and toothache. Acetaminophen over dosage is considered as one of the major causes of hepatic toxicity. The current study aimed to investigate the protective effect of corn silk methanolic extract (CSME) against acetaminophen (APAP)-induced hepatic toxicity. Therefore, the present study was carried out on 40 male Wistar albino rats, which were randomly allocated into four groups (n=10). Control group; orally administered with 0.9% normal saline. CSME group, orally received CSME, 400 mg/kg BW daily for 5 weeks; APAP group , orally administered with a single dose of APAP, 2g/kg BW; APAP+ CSME group , orally administered with CSME as in CSME group, followed by a single oral dose of APAP as in APAP group. The results of this study revealed that APAP caused a significant elevation in alanine  transaminase (ALT) and aspartate transaminase (AST) activities. Also, APAP caused significant increases in of  malondialdehyde (MDA) and nitric oxide (NO) concentrations compared with control group. However, pre-treatment with CSME restored all biochemical parameters toward the normal levels as the control group. In conclusion, oral administration of CSME protected rats against APAP hepatic toxicity through its antioxidant protective mechanisms.