Lead intoxication resulted to change the rat's liver histopathological and biochemical profiles. Pb participated in the liver damage and dysfunction that confirms through the elevation of destroyed and dis-normal shaped hepatocytes, striking lead acetate residue in Kupffer cells, hyperplasia of Kupffer cells, a high number of bi-nucleated hepatocytes, congested sinusoids, and autolytic cytoplasm (Fig. 1a and Table 3). Further, raising ALT, AST, ALP, and GGT activities and TB quantity along with the reduction of total protein, Alb, and globulins levels (Table 1) in the Pbt Group not only satisfies liver damage but also indicates liver dysfunction. The preventive effect of the treatment on the Pb motivated histological changes of the rat’s liver (Fig. 1b) and its diminishing effect on the liver dysfunction biochemical parameters (Table 1) validates its protective against Pb related hepatotoxicity and its recovery effect on liver function. In the research, similar to previous studies ALT sera activity was more than AST resulting in Pb exposure [5, 17]. Pb via the accumulation in the liver, free radical generation, endogenous antioxidants reduction, and bio-membrane injury participates in liver damage and dysfunction [5, 18]. Here, the Pbt group had the highest Pb, oxidative stress markers (AOPP and MDA), and inflammatory markers (NF-kβ, IL-1β, and MPO) along with the lowest antioxidant markers (total glutathione, GSH/GSSG, FRAP, CAT, and PON) in the sera and the liver homogenates. The hepatic NF-kβ is a principal coordinator in liver physiology and diseases [19] and a decrease in NF-kβ signaling is a potential target for the hepatoprotective agents proceeding [20]. Pb takes part in liver dysfunction by upping the hepatic NF-kβ pathway resulting in an increase in oxidative stress and inflammation [5]. elevating IL-1β has a pivotal role in liver disease through the of raising the hepatic NF-kβ expression as a consequence of oxidative stress [21]. In addition, an increase in MPO activity in liver tissue results in liver injury due to raising MDA [22] and AOPP [5] as pointers of lipid peroxidation and protein oxidation, separately. The lessen of Pb, oxidative stress, and inflammatory markers ,as well as more antioxidant markers in Pbt (B3) rats (Table 2), confirms the chelating, antioxidant, and anti-inflammatory properties of B3. The treatment had a hepatoprotective effect through the reduction of NF-kβ signaling (Fig. 2), its stimulators, and MPO activity (Table 2). Reduced glutathione powerfully retards the Pb reactive toxic metabolites [23]. Hence, lifting GSH/GSSG is a profitable strategy versus lead induced hepatotoxicity. PON-1 has an antioxidant effect against lipid peroxidation in the cell membranes and lipoproteins [24]. In this study, B3 raised total glutathione and GSH/GSSG in normal and Pb groups (Table 2) due to elevating glutathione synthesis and glutathione reductase activity in N (B3) and Pbt (B3). Moreover, an increase in GSH level causes a decrease on Pb levels in the sera and liver homogenates of the cited groups by elevating Pb excretion [5, 25]. Furthermore, an elevation in GSH decreases lipid peroxidation by upping glutathione peroxidase activity [26]. The signs of liver histopathological alternations in this research are alike to previous studies [5, 27]. We reported for the first time the effect of B3 on the cited liver histopathological and biochemical parameters in the lead intoxication rat model. Lately, the hepaprotective effect of nicotinic acid in a rat model of zinc and nicotinic acid deficiency via its raising effect on antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and CAT) was represented [28]. In addition, the ameliorating effect of niacin on renal failure in rats via its reducing effect on the renal NF-kβ signaling and lipid peroxidation was reported [29].