Background: Acute Thallium (Tl) toxicosis is still a health problem, worldwide. Oral administration of Prussian blue (PB) is the antidotal treatment of election. On the other hand, metallothionein (MT) is a low-molecular-weight protein, with high content of cysteines (25–30%). MT is able to chelate metals as an efficient endogenous mechanism of detoxification. It is also a potent antioxidant. Methods: In this study, we tested the ability of MT at two doses (100 and 600 µg/rat), administered alone or in combination with Prussian blue (PB) (50 mg/kg) to decrease thallium (Tl) toxicity. A sublethal dose of Tl (16mg/kg) was injected i.p. to male Wistar rats. Antidotes were administered twice-daily, starting 24h after Tl injection, for 4 days. Tl concentrations were analyzed in body organs and brain regions, 5 days after Tl injection. Results: Results showed a diminution (p<0.05) of Tl concentrations in all organs by effect of PB alone or in combination with MT-100 and MT-600, whereas MT-100 only decreased Tl concentrations in testis, spleen, lung and liver. Likewise, Tl in brain regions was also diminished (p<0.05) by effect of PB and both MT-100 alone or in combination in most of the regions analyzed (p<0.05). The greatest diminution of Tl was achieved when the antidotes were combined. Plasma markers of renal damage, increased after Tl administration. Both PB and MT, either alone or in combination, prevented the raise of renal markers of Tl Toxicity. Conclusions: Our findings demonstrate that the combined treatment of PB + MT is a good antidotal option against thallotoxicosis.