A number of enzymes and transcription factors have been correlated with disease etiology. In this study, involvement of cyclooxygenase-2 and inducible-nitric oxide synthase is examined during diethylnitrosamine (DEN)-induced hepatic injury and cloudy apple juice (CAJ) supplementation. Liver injury was administered in rats by single dose of DEN (10 ml/kg bwt of 1% DEN), while 10 ml/kg bwt CAJ daily was given after 2 h of latency in DEN-treated animals for two weeks. CAJ was characterized by HPLC and subsequently examined for antioxidant power. During the course of treatment liver function, collagen (hydroxyproline), malondialdehyde, protein oxidation, antioxidant enzymes, ATPases, nitrite levels were investigated along with liver histopathology and electron microscopy. COX-2 and iNOS proteins were also localized in liver specimens. The results demonstrated rich polyphenols and antioxidant activity in CAJ. CAJ supplementation significantly restored liver biochemistry and anatomy as revealed by the refurbished investigated parameters. CAJ treatment also declined COX-2 and iNOS activities in injured animals. Electron microscopy demonstrated rejuvenated hepatocytes, Kupffer cells, RER, mitochondria and nucleus in CAJ supplemented animals. The novel outcomes of this study suggest that CAJ potentiates hepatoprotection by stimulating antioxidant power and regulating the COX-2 and iNOS proteins in the liver during experimental liver injury.