Lead (Pb)-induced nephrotoxicity has been recognized as a human major public health problem. The aim of the present study is to investigate the possible protective effects of zinc (Zn) or/and quercetin on Pb-induced histologic and ultrastructural changes in the rat kidney. For this purpose, 35 adult male albino rats (Rattus norvegicus) were divided equally into 5 groups, each of 7 rats. Group I (control group): rats received physiological saline intraperitoneally (i.p.) and distilled water orally for 14 consecutive days. Group II (Pb-treated group): rats were orally administered lead nitrate (20 mg/kg body weight/day) for 14 consecutive days. Groups III (Zn and Pb-treated group): rats were administered zinc chloride (2 mg/kg body weight/day, i.p.) 1 hour prior to Pb administration, for 14 consecutive days. Group IV (quercetin and Pb-treated group): rats were orally administered quercetin (50 mg/kg body weight/day), 1 hr prior to Pb administration, for 14 consecutive days. Group V (Zn-quercetin and Pb-treated group): rats received Zn, quercetin and Pb at the same doses, periods and ways of administration mentioned above. The kidney structure of Pb-treated rats revealed swollen, congested glomeruli, adhesion of the glomerular tufts to Bowman's capsules and obliteration of the urinary spaces. Obliteration of the lumina of many glomerular capillary loops was also seen. Some of the renal tubules (mainly the proximal tubules) exhibited luminal dilatation with flattening of their lining epithelial cells, while the other tubules appeared swollen and necrotic with pyknotic or karyolytic nuclei. Exfoliated damaged epithelial cells were also observed within the tubules' lumina. Interstitial inflammatory cell infiltration, intertubular haemorrhage and an increase in the number of fibroblasts were also detected in the degenerated tissue. Ultrastructurally, Malpighian corpuscles showed electron-dense nuclei of the parietal and endothelial cells, complete fusion and effacement of some foot processes of the podocytes, focal thickening of the glomerular basement membrane and an increase in the number of mesangial cells. Many proximal convoluted tubules revealed apoptotic cells with marginal condensed chromatin of their nuclei, fused distorted mitochondria, increased lysosomes, multiple cytoplasmic vacuoles, destructed microvilli of the brush border, and dilated basolateral invaginations. However, simultaneous administration of Zn or quercetin plus Pb partially protected the renal tissues against the toxic effects of lead. On the other side, the combination of Zn and quercetin offers additional protective effects against Pb-induced nephrotoxicity in rats. It is concluded from the present study that co-treatment with Zn and quercetin has a better renoprotective effect than that induced by Zn or quercetin alone.