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Metallothionein (MT), a low-molecular-weight, cysteine-rich, zinc-binding protein, has an important effect in the detoxification of various metals. However, extra Zn7-MT protects aginst the cellular toxicity of lead in rat primary hepatocyte (RPHC) culture has seldom been examined thoroughly. This study was therefore designed to determine the effects of extra Zn7-MT on the toxicity of lead in rat primary hepatocyte culture. Hepatocytes were grown in monolayer culture for 24 h and Zn7-MT was subsequently added for 24 h. RPHC were exposed to different concentration of lead for 24 h. Cytotoxicity was assessed by enzyme leakage and loss of intracellular K+. Meanwhile, the subcellular distribution and accumulation of lead was studied, and the protactive effect on the cellular toxicity of lead in RPHC culture in the present of Zn7-MT was investigated. The results showed that the toxicity of lead was significantly less in the presence of Zn7-MT. The hepatocelluar uptake and accumulation of lead have markedly altered. In the cytosol of control cells, the lead was bound mainly to high-molecular-weight proteins whereas the lead was mainly associated with MT in the presence of extra Zn7-MT.