Environmental pollutants, particularly lead, pose a serious threat to human and animal health that causes disturbances of several functions, including hepatotoxicity. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. This study was carried out to investigate the protective efficacy of Juglans regia vegetable oil (JRVO) against the hepatotoxicity induced by lead. To achieve this aim, adults male rats were treated for 10 days with Pb (0.344 g/kg bw) associated or not with JRVO (0.9 g/kg bw). The rats intoxicated by lead exhibited oxidative stress determined by TBARS, protein carbonyls, liver tumor necrosis factor‐α (TNF‐α), caspase‐3, and antioxidant status: SOD, CAT, GPx, and GSH. Administration of lead increased the levels of plasma hepatic markers (AST, ALT, LDH) and bilirubin, the lipid profiles (total cholesterol, triglycerides, VLDL‐Ch, LDL‐Ch levels, TBARS, NOx, and PCO), the plasmatic lipase activity and the inflammatory markers, while the plasmatic ALP decreased. Coadministration of JRVO restored all the hepatic markers, the lipid profiles and the antioxidants to near‐normal values and lowered the plasmatic lipase activity as well as the elevated thiobarbituric acid reactive substances. Hepatic histological studies confirmed the beneficial role of JRVO through the amelioration of all biochemical parameters. Our results suggest that Juglans regia vegetable oil contains promising substances to counteract the lead intoxication and may be efficient in the prevention of hepatotoxicity complications.