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Background and objective Celastrus hindsii Benth. has been used for generations in Northern Vietnam, for the treatment of disease relating to ulcers, tumors and inflammation without safety evidence. This study's goal is to evaluate the safety of the aqueous extract of leaves of C. hindsii through an acute and semi-chronic toxicity oral administration. Materials and methods In the acute study, a single oral dose (1000, 3000, 5000 and 15000 mg kg-1) of the aqueous of C. hindsii extract were administered to mice and observed for seven days. In the semi-chronic study, rabbits were administered daily with 1000 and 3000 mg kg-1 of the extract for 35 days. Hematological and biochemical analyzes were carried out on blood and serum samples collected. Results A single oral administration of 15000 mg kg-1 per day for white mice did not determine the LD50 dose. At doses of 1000 and 3000 mg kg-1 for 35 days, the extract from C. hindsii induced neither clinical symptoms of rabbits nor significant changes in hematological parameters such as; total blood cells, hemoglobin concentration, white blood cells and platelets. The quantity of aspartate transaminase (AST or GOT), alanine transaminase (ALT or GPT) of rabbits in the experimental and control group did not differ (p> 0.05). Liver and kidney organizations were also not affected adversely. Conclusion The results indicate that the oral administration of C. hindsii extract did not produce any significant toxicity in mice, therefore, it is recommended to be used safely for traditional medical practices and modern pharmaceutical applications.