4-nitrophenol (PNP) is used to make drugs, fungicides and insecticides based on parathion, it is also one of the four nitrophenol derivatives of DEP and considered EDCs . PNP is known to have various harmful physiological effects. This research was conducted to study the effect of chronic exposure to PNP on liver health status in 28-day-old male Japanese quails orally administered PNP (0, 0.01, 0.1, 1 mg/kg body weight) for 2.5 months, with samples taken every 15 days and histopathology (H&E and PAS), PCNA, apoptosis detection and serum level of 'AST were then used to study the impacts of the PNP. Basal mRNA level of cytochrome P450 enzymes (CYP 1A4, 1A5, 1B1), liver Ho-1, GST and AH receptors in vivo and in vitro from liver hepatocytes, 24 h incubation with PNP at different concentrations measured using the RT-PCR method. The results showed that chronic exposure to P-nitrophenol caused liver weight disruption accompanied by histopathological signs, namely lymphocyte aggregation, blood vessel congestion, hepatocyte degeneration and necrosis at different degrees, which which had repercussions on the plasma concentrations of liver enzymes (ASAT) where they increased everywhere. AST especially at 2.5 months where the medium dose reported 503.0 U/l and the high dose 350.0 U/l compared to 204 U/l in the control group also a significant increase in PCNA (P < 0.01 ), glycogen accumulation (P < 0.05) and apoptotic cells. (P < 0.01) were reported. In vivo, after 2 months of PNP administration, birds show overexpression of CYP1A4 (approximately 1.5 to 2 times higher), 1B1 enzyme (approximately 5 to 10 times higher), AhR (approximately 2 to 4 times higher) and HO-1 than the other enzymes, GST and 1A5, which showed no change compared to the value of the control group but with continuous chronic administration of PNP over the entire regulation negative in all living ...... middle of paper ...... ure to ethanol and tobacco smoke in relation to the level of expression of the PCNA antigen in pancreatic and hepatic cells rat.52. Yonghui Zhang, Yuanguo Piao, Yansen Li, Meiyan Song, Pingli Tang, ChunMei Li., 2013. 4-nitrophenol induces Leydig cell hyperplasia, which may contribute to the differential modulation of androgen receptor expression and estrogen receptors - α and -β in men. rat testicles. Toxicol. Letters 223, 228– 23553. Yue, Z., She, R., Bao, H., Li, W., Wang, D., Zhu, J., Chang, L., Yu, P., 2011. Exhibition 3-methyl-4-nitrophenol affects testicular morphology and induces apoptosis of spermatogenic cells in immature male rats. Res. Veterinarian. Sci. 91, 261-8.54. Zhang. HF, Lin.XH, Yang.H, Zhou. L.C., Guo. YL, Barnett. JV and Guo. ZM, 2012. Regulation of aryl hydrocarbon receptor activity and expression by ethanol in mouse hepatic stellate cells. Alcohol C