Pesticides play an important role in hepatotoxicity and liver damage. Lycopene is known to possess several beneficial properties including; antioxidant and anti-cancer effects. However, there is a lack of relevant information on its importance in chronic fungicide-induced hepatotoxicity. Therefore, our study was to assess the protective role of lycopene on metalaxyl-induced oxidative stress in liver tissue of male rats. The experiment was designed for 8 weeks and male albino rats were divided into 3 groups (n = 14). Group 1 served as normal control (with no treatment), group 2 metalaxyl exposed group; rats received metalaxyl at a dose level of 1/10 LD50 (130 mg/kg b.wt) orally three times per week, group 3 metalaxyl and lycopene;rats received metalaxyl (130 mg/Kg b.wt) orally three times per week and treated daily with lycopene (10 mg/kg b.wt/ orally). Our data showed that metalaxyl significantly increase serum Alanine AminoTransferase (ALT), Aspartate AminoTransferase (AST), Alkaline Phosphatase (ALP) activities, enhanced levels of L-MalonDiAldehyde (L-MDA), Nitric Oxide (NO), MyeloPerOxidase (MPO) and up-regulation of nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interlukin-6 (IL-6), caspase-8 gene expression, induced DNA damage. Meanwhile, down-regulation peroxisome proliferator activated receptor alpha (PPAR-α) and decreased the liver superoxide dismutase (SOD) and catalase (CAT) activities. Lycopene treatment was restored the hepatic antioxidant status which had indicated the significant protective effect against metalaxyl induced hepatotoxicity and finally confirmed by histopathologicaland immunohistochemical studies.