Abstract: This study investigated the influence of dietary calcium supplementation to reduce the toxicity of sublethal lead concentration in Nile tilapia with emphasis on biochemical and histopathological analysis. The values of 24, 48, 72 and 96 h LC50 of lead to tilapia were 247.51, 197.47, 193.36 and 182.38 mg L-1, respectively. Therefore, lead concentration tested in the sublethal experiment was 45 mg L-1, which correspond to 25% of the 96 h LC50. Fish were fed with 0, 20 and 60 mg Ca2+ g-1 food for 30 days. In the gills of Pb treatment, edema, lamellar cell hyperplasia, epithelial lifting, lamellar fusion and aneurysm were observed. In the liver, there were blood congestion in sinusoids, vacuolation of hepatocytes and necrosis. In the kidney, glomerulus’s atrophy, tubular swelling and also necrosis were seen. The structural damages could be correlated to the significant increase (p≤0.05) in aminotransferase activities. Fish fed with Ca2+ supplemented diets showed slightly alteration when compare the only Pb treatment groups. These results indicated that dietary Ca2+ will be protective in reducing Pb burdens in fish exposed to environments contaminated with waterborne Pb.