Abstract: Objective To investigate the protective effect of exogenous metallothionein-1 (MT-1) against liver injury induced by mercuric chloride poisoning in Brown-Norway rats. Methods Male Brown-Norway rats (n = 42) were randomly divided into six groups (n = 7 per group), including normal control, model control, positive control, and low-, medium-, and high-dose MT-1 groups. Except for the rats in the normal control group, the rats in all other groups received subcutaneous injections of 1 mg/mL mercuric chloride solution (1.0 mg/kg) every other day for 14 days (7 injections total). The positive control group rats were intramuscularly injected with 2.5 mg/mL sodium 2, 3-dimercapto-1-propanesulfonate (DMPS) at 5 mL/kg every 2 days. Rats in the low-, medium-, and high-dose MT-1 groups received MT-1 via oral gavage at concentrations of 0.032, 0.080, and 0.160 mg/mL (5 mL/kg body weight), respectively, once daily. The normal control and model control groups received equivalent volumes of 9 g/L sodium chloride solution (mass-volume concentration). After the experiment, rat body weight and liver wet weight were measured, and the liver index was calculated. Gross pathological changes of the liver were observed, and serum alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), bilirubin, total protein, globulin, and albumin-to-globulin ratio were determined as indicators of liver function. Results Compared with the normal control group, the mercuric chloride-treated groups of rats showed varying degrees of poisoning symptoms, including reduced body weight, increased liver index, significant elevation in serum ALT, GGT, and total bilirubin levels, and significantly reduced total protein and albumin/globulin ratio. Compared with the model control group, the medium and high dose MT-1 groups and the DMPS group showed a significant lower serum ALT and GGT levels (P < 0.05). All MT-1 dose groups demonstrated significantly higher total protein levels (P < 0.05), and the high-dose MT-1 group also showed a significant recovery in albumin/globulin ratio and total bilirubin level (both P < 0.05). Conclusions Exogenous high-dose MT-1 could alleviate some mercuric chloride-induced liver function abnormalities, with comparable efficacy to DMPS, while also improving total protein level in the model rats.