Objective To study the toxicity of a single administration and 3-month repeated administration of An’ erning (AEN) granules in juvenile SD rats, and evaluate the long-term safety in children. Methods 20 juvenile SD rats (3 ~ 4 weeks) were given the maximum administration dosage ( 240 g crude drug / kg). This was followed by an observation of toxicity reactions and death for 15 days. Juvenile SD rats (200) were divided into vehicle control, Aconitum tanguticum control, low-dose, middle-dose, and high-dose groups. Each group was composed of 40 rats ( half male and half female), each of which was given purified water, A. tanguticum (5. 5 g crude drug / kg), and AEN (3, 11, and 40 g crude drug / kg), all in a volume of 10 mL/ kg, for 91 days. Food intake and body weight were measured, and hematology, biochemistry, coagulation, urine, ophthalmologic, and histopathology examinations of 5,10 and 5 rats for each sex in each group were conducted mid-administration, upon drug withdrawal, and 4 weeks after withdrawal. Results No obvious toxic effects or deaths were recorded after the single administration of AEN. After the 3-month repeated administration of AEN, male rats in the high-dose group had decreased body weights, decreased food intake, reversibly increased NEUT count, NEUT ratio, MONO count, MONO ratio, and ALB, and reversibly decreased AST, Na⁺ , and Cl^- . Conclusions There were no obvious toxicity reactions in young rats given AEN granules. The relative safe dosage of AEN was 40 g crude drug / kg, and the no observed adverse effect level (NOAEL ) is 11 g crude drug / kg. The clinical administration of AEN is safe.