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The purpose of this study was to compare the biocompatibility of amalgam, gray MTA and white MTA in the connective tissue of rats. We used 45 Sprague-Dawley rats in this study. The rats were divided into three groups. Root end filling materials were placed in polyethylene tubes and inserted into the rats' connective tissue through incisions. The rats were sacrificed after 3 days, 1 wk, and 3 wk, respectively. Histologic samples were sectioned in 5-μm thicknesses and stained with hematoxylin and eosin. Kruskal-Wallis test was used for statistical analysis. The results showed that after 3 days, white MTA was more biocompatible than gray MTA and amalgam. After 1 week, gray MTA was more biocompatible than white MTA and Amalgam. After 3 wk, there were no significant differences between experimental groups and the control group.