Abstract: The present study is carried out in order to explore the capability of copper sulfate (CuSO4) and lead acetate (CHCOO)3 Pb in inducing chromosomal aberrations in aquatic organisms. To achieve such a purpose, Oreochromis niloticus was chosen as a test material for the study. The LC50 of the two chemicals was determined and the data indicated that LC50 of copper sulfate (CuSO4) and lead acetate (CHCOO)3 Pb were 40.6 and 422.5 mg L-1, respectively. The effect of both chemicals on fish chromosomes and mitotic indices was investigated and the results revealed that gill cells of the treated fish by copper sulfate and lead acetate displayed lower mitotic activity than that of the control group, both pollutants were found to be positive inducer of macro-DNA damage which represented by different types of aberrations e.g., chromatid deletions, chromatid breaks, gaps, fragments, stickness, translocations, ring chromosomes and centromeric attenuation. We also observed that chromatid deletion, stickness and fragments were more frequent than other chromosomal aberrations.