We histologically examined the effects on the periapical tissue of various dental filling materials applied as retrofillings in rats and compared them with those of amalgam. The 4-META-TBB resin Superbond and the light-cured composite resin produced the least severe inflammatory reaction, with the greatest amount of new bone. In these specimens, regeneration of a part of the periodontal ligament was also observed. These results indicate that these materials might be very biocompatible and thus foster the natural regeneration of the periapical tissue.