The purpose of this histopathologic study was to assess and compare the subcutaneous connective tissue reaction to a new root canal filling material, Resilon and guttapercha. The test materials were directly inserted subcutaneously into the dorsal connective tissue of Wistar albino rats. Histo pathological examinations were done at 7, 15, 30, and 60 days after the implantation procedure. The presence of inflammation, predominant cell types, and the thickness of fibrous connective tissue adjacent to each inserted sample were recorded. There were no differences in tissue reaction between Resilon cone material and gutta-percha cone groups for first three observation periods (p > 0.05). However, there were highly significant differences among observation periods within both groups (7, 15, 30, and 60 days) (p < 0.01). The tissues showed high tolerance to Resilon and gutta-percha at the 60th day. Resilon may serve as an alternative to gutta-percha in terms of biocompatibility. (C) 2007 Wiley Periodicals, Inc.