The aim of this study was to investigate the effect of yeast metallothionein (MT) with known lead-expelling and liver-protecting properties on mice in which, chronic lead poisoning was induced by lead acetate solution gavage for 35 days. Dimercaptosuccinic acid (DMSA) and animal MT (rabbit liver Zn-MT) were used as controls and MT was administered to the mice. Subsequently, the weight, blood lead levels, and liver function indices were measured and a routine blood tests were conducted to observe the severity of pathological changes in the liver tissue. Compared with that of the control group, the weight of MT-treated groups was not significantly different. The blood lead level in high-dose MT-treated group was significantly decreased, while the levels of white blood cells (WBC), mean corpuscular volume (MCV), and hemoglobin (HGB) were significantly increased (p < 0.05). However, there were no significant differences in granulocyte (GR) counts between all groups (p > 0.05). The levels of glutamate pyruvate transaminase (GPT) in all MT-treated groups were significantly decreased (p <0.05). Meanwhile, the levels of glutamate oxaloacetate transaminase (GOT) in the high-dose MT-treated group were significantly decreased (p <0.05), pathological changes in liver tissue were ameliorated, and the degree of improvement was higher than that of DMSA group. Two types of yeast metallothionein exhibited lead-expelling and liver-protecting effects on mice with chronic lead poisoning, similar to animal metallothionein.