The aim of the present study was to evaluate the possible protective effects of ginger, an anti-inflammatory agent, against metalaxyl induced liver toxicity in male rats. In total, 42 albino rats were fed a standard rodent diet and divided into 3 equal groups. Group I (normal control group): rats administered distilled water. Group II (metalaxyl exposed group): rats received 1/10 LD50 (130 mg/kg b.wt) orally three times per weeks for 8 weeks. Group III (metalaxyl+ginger treated group): rats received metalaxyl (130 mg/kg b.wt) and treated with ginger (100 mg/kg b.wt/day/orally). Metalaxyl caused significant increase in liver tissue nitric oxide (NO) and L-Malondialdehyde L-MDA levels associated with upregulation of nuclear factor kappa B (NF-kB), tumor necrosis factor alpha (TNF-α) and Caspase-8 gene expression and increase DNA damage in liver tissue while down-regulation in Peroxisome proliferator activated receptor alpha PPAR-α. In addition, the results demonstrated that ginger might ameliorate metalaxyl-induced liver damage by decreasing oxidative stress. Moreover, ginger exhibited protective action against the metalaxyl-induced histopathological and immunohistochemical changes in liver tissues of male rats.In conclusion, ginger was found to be effective in protecting rats against metalaxyl-induced liver damage by anti-inflammatory mechanism.