The cleaning and shaping of root canals is one of the most important proccesses in endodontics. In many cases, the physiologic or pathologic proccedures can affect the canals. So, using the instruments and materials, which could be applied in cleaning and shaping of narrow canals is necessary. The aim of this study was the evaluation of Iranian and foreign chelating agents on periradicular tissue of cats. After cleaning and shaping of canals in 18 lower canines of cats, the original RC-Prep and an Iranian chelating agents were placed equally in two groups with 9 teeth in each one. The patency of canals preserved for materials leakage. In 3 lower canines of cats, phosphoric acid was placed as positive controls.3 canine teeth as negative controls had nothing in them. The crowns were sealed and the cats were sacrificed in 1/21/42 days periods after conducting vital perfussions. The teeth samples with their surrounding osseous tissues were gathered and placed in three groups each contained 6 samples. Histologic preparations were done and the tissue reactions to these materials were evaluated by counting the proliferative inflammatory cells. Also the morphometric analysis for these samples was done. The inflammatory reactions of these materials (the original RC-Prep. & the Iranian chelating agent) were not statistically different. Both of these materials were different in inducing tissue reactions in comparison with those of positive and negative controls, and these differences were statistically important.