Different materials have been suggested for endodontic surgeries. One of the most important characteristics of filling materials is their biocompatibility.Aim: The aim of this research was to evaluate the biocompatibility of four different root end filling materials.Material and Methods: In-this study, 20 male Guineanpigs from English--short hair breed, weighing 600-700 grams, were selected. The animals were classified into two groups. In the first group, amalgam and composite and in the second group MTA and Glass Ionomer were examined. The testing materials were shaped into cylindrical form with I mm diameter and 1.5 mm height. After general anesthesia, two cavities with I mm diameter and 2 mm depth were prepared in parasymphysis area of animal jaw. The prepared materials were implanted in these cavities and the flaps were sutured. After 80 days, the animals were sacrificed and the dissected bones, with implanted materials inside them, were sent for histological evaluation. The histological findings were statistically analysed by Kruskal Wallis and Y, 2 tests.Results: No significant differences were shown in the degree of inflammation, the type of inflammatory cells adjacent to the tested materials and the type of tissue response, induced in the vicinity of these four materials during 80 days.Conclusion: Regarding biocompatibility, there was no significant difference among amalgam, composite, MTA and glass Ionomer in endodontic surgeries.