Background: Cadmium (Cd), one of the most abundant heavy metals, is extremely toxic to both humans and animals. hIt is well known that zinc (Zn) administration reduces Cd-induced toxicity and that metallothioneins can have a protective effect in biological systems to mitigate Cd toxicity. Objective: The aim of the current study to determine if Zn administration affected the induction of MT-1 and MT-2 in the liver tissue in mice exposed to Cd. Materials and methods: Metallothionein protein (MT) level in the tissue of male mice were detected using the anion -exchang high-performance liquid chromatography coupled (HPLC)assay and immunohistochemical staining. Results: Single treatment to zinc or cadmium increase the level of MT in the liver, but zinc chloride treated significantly increase the level of MT after sub chronic treatment. Conclusion: Zinc pre-treatment with increasing the concentration of the dose of cadmium used in the co-treatment, and both of them may have worked together to induce a significant increase in protein synthesis to exceed the high toxicity of cadmium, by inducing an increase in MT protein synthesis.