OBJECTIVE: To investigate toxic reaction of Compound zedoary turmeric oil cream in experimental rats with long-term consecutive transdermal administration, and to provide reference for safe use of it in the clinic. METHODS: 60 SD rats were randomly divided into blank control (cream matrix) group, Compound zedoary turmeric oil cream intact skin and damaged skin low-dose and high-dose (5%, 10%) groups, with 12 rats in each group, half male and half female. All of them were given relevant medicine twice a day. 92 d consecutive medication later, general situation of rats were observed, and body weight, blood routine (WBC, RBC, HGB, LYMPH, etc.) and blood biochemical indicators (AST, ALT, PA, etc.) were all detected; systematical observation of organs, organ coefficient calculation and histopathology examination were carried out. RESULTS: There was no statistical significance in those indicators between Compound zedoary turmeric oil cream groups and blank control group (P>0.05), except hemoglobin decreased in intact skin low-dose group, while hemoglobin decreased, LYMPH and PA increased in damaged skin high-dose group (P<0.05). Pathology results showed that Compound zedoary turmeric oil cream had no significant toxicity for the main organs. CONCLUSIONS: Compound zedoary turmeric oil cream has no long-term toxicity to experimental rats.