Today metal pollution is rapidly increasing with advances in technology and industry. Due to their bioaccumulative and nonbiodegradable properties, heavy metals are important contaminant of aquatic organism all over the world. Metal toxicity causes oxidative damage such as DNA damage, enhanced lipid peroxidation, the oxidation of protein sulfydryl groups and enzyme inactivation in the metabolism. In this study, we investigated in vitro effects of some metals on carbonic anhydrase enzyme which has vital role in fish metabolism. For this aim, The enzyme, was purified from gills of tuna with a specific activity of 1062 EU/mg proteins and 31% yield using Sepharose 4B– aniline–sulfanilamide affinity chromatography method. SDS–polyacrylamide gel electrophoresis showed a single band corresponding to a molecular weight of approximately 29 kDa. Inhibitory effects of metals (Ag+, Cu2+, Pb2+, Zn2+, Cd2+, Co2+) on CA activity were determined at different concentrations using the hydratase method under in vitro conditions. Consequently, in vitro inhibition rank order was determined as Ag+> Cu2+> Pb2+> Zn2+ > Cd2+> Co2+. From these results, we showed that Ag+ is the most potent inhibitor of CA enzyme.