The present study was aimed to assess the hepatoprotective activity of ethanolic extract of Sesamum indicum Linn. seeds against Paracetamol-induced liver damage in rats. Paracetamol-induced liver damage was produced by the treatment of Paracetamol (2g/kg/day, p.o) on three consecutive days for seven days. Other groups of rats were pretreated with two doses of Sesamum indicum (400mg/kg and 700mg/kg) and silymarin (25mg/kg, bw, p.o.) 30 min prior to Paracetamol ingestion. Liver damage was assessed using various biochemical parameters viz. Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyurvate Transaminase (SGPT), Alkaline phosphatase (ALP), Acid phosphatase (ACP), Total Protein, Albumin and Total Bilirubin along with histopathological examination of liver tissue. There was a significant increase in serum enzymatic levels of Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyurvate Transaminase (SGPT), Alkaline phosphatase (ALP), Acid phosphatase (ACP) and Total Bilirubin with a decrease in Total Protein and Albumin level, in Paracetamol treated animals, reflecting liver injury. Pretreatment with two different doses (400mg/kg and 700mg/kg) of Sesamum indicum produced significant reversal in the above biochemical parameters and reduced histopathological scores of fatty degeneration, centrilobular necrosis with significant evidence of regeneration. The results of the study indicate that the extract of Sesamum indicum possesses significant protection against Paracetamolinduced hepatocellular injury.