OBJECTIVE: To investigate the safety of Polyisobutylene (PIB) Gutong plaster by transdermal administration. METHODS: 66 rabbits were randomly divided into a normal group, a group with intact skin and a group with damaged skin. The latter two groups were respectively re-divided into PIB group, the groups of low, medium and high-dose PIB Gutong plaster and Gutong plaster group. An acute toxicity test was conducted on the rabbits, which 14 d of continuous observation was made 24 h after transdermal administration. Another 60 rabbits were divided into several groups as above except for a normal group. A single primary skin irritation test was conducted on them, where skin irritation reactions were recorded 6 h after a single administration based on intra-individual left/right self comparison method. 70 guinea pigs were randomized into a negative control group (vaseline), a PIB group, a positive control group (2,4-dinitrochlorobenzene), a Gutong plaster group and the groups of low, medium and high-dose PIB Gutong plaster, which were dosed for sensitization, followed by a skin sensitization test. RESULTS: No obvious toxicity symptoms could be seen after administration of PIB Gutong plaster. The rabbits’ intact or damaged skin had no irritation response to PIB and low and medium-dose PIB Gutong plaster. PIB Gutong plaster caused no irritation response in the rabbits’ intact skin, but slight irritation in damaged skin 1 h after administration. The allergic reaction incidence of the positive control group of guinea pigs was 100% while that of any other groups was 0. CONCLUSIONS: The PIB Gutong plaster is safe for transdermal administration.