The purpose of this study was to analyze the sealing ability of various filling combinations in a 90 days period using fluid transport and glucose penetration models. Premolars (n = 108) were filled with either gutta-percha (groups 1-4) or Resilon (groups 5-8) core materials combined with AH Plus (groups 1, 3, 5, 7) or Epiphany (groups 2, 4, 6, 8) sealers by using cold lateral compaction (groups 1, 2, groups 5, 6) or System B with Obtura II (groups 3 4, groups 7, 8). The sealing ability of each sample was evaluated through glucose and fluid penetration models. Penetration values of 90 days were statistically analyzed With three-way analysis of variance (ANOVA)and Duncan's Multiple Range tests (P < 0.05). No significant differences were found among the penetration values when the fluid filtration model was used (p > 0.05). On the contrary, statistically significant differences were obtained among the groups with the glucose penetration model (p < 0.05). AH Plus/Resilon/cold lateral compaction group had better sealing ability than the other combinations tested with the glucose penetration model. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 92B: 261-267, 2010