This study aimed to assess the hepatoprotective activity of ethanol (90%) extract of Blepharis persica seeds (BPEE) in rats. The plant extract showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity as judged from the serum marker enzymes and histopathological studies on liver tissues. The acetaminophen-induced group shows a significant rise in the serum enzymes. Treatment of rats with different doses of plant extracts significantly altered serum marker enzymes levels to near normal against acetaminophen treated rats. The activity of the extracts was comparable to the standard drug, silymarin. Histopathological changes of liver sample were compared with respective control. Results indicate the hepatoprotective properties of Blepharis persica against acetaminophen induced hepatotoxicity in rats.