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.