AbstractAimTo evaluate the influence of different apical enlargement protocols on the radiographic and histological healing of apical periodontitis in rats.MethodologyApical periodontitis was induced bilaterally in the mandibular right and left first molars of 24 Wistar rats by pulp exposure to the oral cavity for 3 weeks. A standard serial root canal preparation technique was performed in the molar of one side, whilst the opposite side was the control group. Rats were randomly divided into three experimental groups (n = 8), according to the diameter of apical enlargement during root canal preparation: K‐files size 20 (EG1), size 25 (EG2) and size 30 (EG3). Each animal was its own positive control, because the opposite arch remained untreated. Root canals were filled with a standard technique. After 3 weeks, the animals were euthanized. The main outcome of apical periodontitis healing was evaluated radiographically (mm2) and histologically (ordinal scores of inflammation) using a HE staining technique. The measurement of effect was obtained between the three experimental groups by carrying out generalized estimating equations, with Poisson regression with robust variance, pairing each experimental group with its respective control group within animals, adjusted for the mean within animal differences, with α = 5%.ResultsThe mean and standard deviations of radiographic apical periodontitis size (mm2) and intensity of histological inflammatory scores were, respectively: EG1 (0.44 ± 0.27; 2.25 ± 0.46), EG2 (0.33 ± 0.10; 2.50 ± 0.53) and EG3 (0.22 ± 0.08; 2.63 ± 0.74). After 3 weeks, a significantly more favourable radiographic repair was observed when larger apical enlargement was performed (EG3), compared to EG1 and EG2 (P = 0.001). All experimental groups were associated with a significant difference on the radiographic and histological healing of apical periodontitis compared with its respective control group.ConclusionUnder the experimental conditions of this study, a larger apical enlargement protocol favoured a more rapid radiographic repair of apical periodontitis in rats after a 3‐week follow‐up.