Background and Objective: Some evidence about the relationship between heme oxygenase and many cancers is available. Heme oxygenase has anti-apoptotic effects and contributes to tumor growth. The aim of this study was to evaluate the effect of heme oxygenase on melanoma tumor cells mitosis and tumor size in C57BL/6 mice. Materials and Methods: B16F10 melanoma cells were injected subcutaneously to 18 C57BL6 mice with 8 weeks of age. Mice were randomly divided into three groups: the first group received Zinc protoporphyrin (Znpp), heme oxygenase inhibitor (n = 6), the second group, hemin (heme oxygenase activator) (n = 6) and the third group((control group) (n = 6)) received diluent injection. They received their injection every other day from the first day of study for 16 days. Tumors were extracted in the 16th day of study. Length and width of tumors were measured and mitotic cell activities were evaluated using immunohistochemistry staining and counting Ki-67 posetive cells. 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