[Objectives] To determine the biological safety of BT protein from Bacillus thuringiensis (Bt) fermentation broth to mammals at high doses. [Methods] Healthy mice were randomly divided into 4 groups with 10 mice in each group. The experimental groups were fed with Bt fermentation supernatant at 0.2, 0.6 and 1.0 mL/kg, respectively, once a day for 7 consecutive days. The blank control group was fed normally without intragastric administration. [Results] There was no significant difference in blood routine and blood biochemical analysis between the experimental group and the control group. After intragastric administration, the mice were dissected, and no obvious pathological changes were found; the heart, liver, spleen, lung and kidney were taken to make tissue sections, and no pathological changes were found by microscopic observation. [Conclusions] Mice can tolerate high doses of BT protein from B. thuringiensis fermentation broth.