In this study we investigated histopathological changes of mice ovarian tissues following long-term administration of copper sulfate and induction of chronic copper poisoning. The study comprised of three different groups of twenty one mice as follows: The first group (Group 100) which treated by gavage with copper sulfate at a dose of 100 mg kg-1 for 5 weeks. The second group (Group 200), which received 200 mg kg-1 copper sulfate by gavage during experimental period (35 days), and control animals (Group C), which received the same volume of distilled water in the same way. The blood samples were obtained from 7 cases out of 21 animals of each group by cardiac puncture at the end of first, third and fifth week. Ovarian lesions were observed in group 100 after 35th day and in group 200 after 21st day. The histopathologic examination revealed widespread ovarian follicle atresia in group 200 after 35th day Atretic follicles had numerous cell debris and inflammatory cells in the antral cavity. In degenerative antral follicles granulose cells degenerated and desquamated into antrum. In some degenerative antral follicles infiltration of inflammatory cells into granulose cell layer and antrum were observed. The histopathlogic data indicate the possibility of adverse effect of copper poisoning on the mice ovarian tissue. Copper might be mediator of the effect of oxidative damage and play an essential role in reproductive system.