OBJECTIVE： To observe the long-term toxicity of piperphentonamine hydrochloride in Beagle dogs， and to evaluate its safety. METHODS： 30 Beagle dogs were evenly composed of male and female and divided into 5 groups， including 4 piperphentonamine hydrochloride groups （6， 12， 24 and 48 mg/kg） and negative control group （5％ glucose， 24 ml/kg）. Beagle dogs were given relevant medicines by ivgtt once a day for consecutive 30 days. And general physiological indexes and 17 blood biochemical indicators were detected， and pathological changes were observed in multiple tissues pathological sections. RESULTS： In 24 and 48 mg/kg piperphentonamine hydrochloride groups， some dogs suffered from transient balance or movement disorders and weakness， and then recovered after some time. In 48 mg/kg piperphentonamine hydrochloride group， plasma level of ALT increased after 15 and 30 days of treatment， compared to before treatment （P＜0.05 or P＜0.01）. Other physiological indicators and the remaining 16 plasma biochemical indexes of piperphentonamine hydrochloride groups could not explain that there was toxicity reaction. In histopathological examination， some dogs of 24 and 48 mg/kg piperphentonamine hydrochloride groups suffered from injection site swelling， and microscopic examination showed edema and chronic inflammatory cell infiltration. CONCLUSIONS： Piperphentonamine hydrochloride has no toxic reaction to Beagle dogs at the dose of 12 mg/kg. It has some wider safe dose range， and this conclusion can provide evidence for clinical drug use.