The biocompatibility and apical microleakage of tricalcium phosphate based Sankin Apatite (SA) Type I, II, and III root canal sealers were investigated. Teflon tubes containing freshly mixed test materials were implanted in the subcutaneous tissue of mice. The observation periods were 24 h, 7, and 30 days, after which the areas of tissue reaction to the implanted materials were histopathologically analyzed. A dye-recovery, spectrophotometric method was used to evaluate apical microleakage. Results showed that the severity of tissue reaction among the tested materials decreased with time and at the end of the observation period both SA Type II and Type III were found more biocompatible than either Type I or Grossman's cement (GC). On the other hand, a fibrous tissue capsule was seen around the implants. There was no significant difference in spectrophotometrically measured leakage among teeth obturated with the test materials.