In this age of modern biology, aquatic toxicological research has provided potential tools for ecotoxicologic investigations. Heavy metals primarily affect protein structures and induce a stress in the organisms. The present investigation was carried out to assess the effect of nickel chloride on the selected organs of the freshwater fish Cirrhinus mrigala and how CaNa₂ EDTA counters its effects as an antidote. Toxicity experiments were conducted for different exposure periods and also in certain tissues namely gill, liver, kidney and muscle. The total protein content, reduced glutathione, glutathione peroxidase and lipid peroxidation were found to be decreased in the nickel chloride treated tissues and the treatment with CaNa₂ EDTA+nickel chloride returned to near normal levels. Histopathological observations also revealed that after the administration of nickel chloride+CaNa₂ EDTA the chelator induced reduction in nickel toxicity. It has also contributed towards reduction in the pathological damage, thus enabling the organs to attain their near normal histological appearance. The present study shown that CaNa₂ EDTA is an effective chelating agent for the removal of nickel and it has proved efficient in restoring both the biochemical variables and pathological features immediately after a sub lethal exposure of nickel chloride in fish. To cite this article: R. Gopal et al., C. R. Biologies 332 (2009).