BACKGROUND: Thiopental and propofol are the most widely used intravenous anesthetics as induction agents in general anesthesia. Thiopental is a very strong alkaline drug, and when it is extravasated, it can cause pain and skin necrosis. Propofol also can cause pain on injection in many populations. Therefore, we planed this study to compare inflammatory reactions of skin tissues after subdermal injections of thiopental and propofol in rabbits. METHODS: Four rabbits were divided into 2 groups: Standard dose (S) group and double dose (D) group. In the S group, thiopental 0.4 ml and propofol 0.4 ml were injected subcutaneously on each side of the posterior proximal ear. In the D group, the dose was doubled to 0.8 ml of each drug and injection was done in the same manner. Skin tissue at the injection sites were excised after 1 day, 3 days, and 7 days. Then each skin tissue slide was examined under an optical microsccpe. RESULTS: In the S group, the inflammatory reaction after the subdermal injection of 2.5% thiopental revealed a more progressed and more severe pattern than 1% propofol. In the D group, the inflammatory reaction after a subdermal injection of 2.5% thiopental revealed a more progressed and more severe pattern than 1% propofol at 3 days, but there was no significant difference in the degree of progression and severity between the 2 drugs at 7 days. CONCLUSIONS: When propofol is extravasated during continuous infusion for maintenance of anesthesia, it can cause distinct inflammatory reaction; though the inflammatory reaction is milder and the possibility of complications is lower than with thiopental.