<p><strong>Objective:</strong> Evaluate, <em>in vivo</em>,<em> </em>the influence of mixing failures on endodontic sealers. <strong>Material and methods:</strong> To alveolus analysis, 80 rats were divided into Sealapex^® and AH Plus^® groups. Within each group, the sealer was subjected to either partial (incomplete homogenization—simulating handling failures) or total mixing (complete homogenization) over two periods of 7 and 30 days (n = 20). The maxillary incisor was extracted and a polyethylene tube containing the sealer was inserted. To quantify edema, 40 male rats were divided into four groups (n = 10). The animals received 2% Evans Blue intravenously, and either AH Plus^® or Sealapex^® was injected subcutaneously. The rats were euthanized after 3 or 6 hours and analyzed in a spectrophotometer (630 ƞm). To analyze the subcutaneous tissue, 20 rats received polyethylene tube implants with the sealers in the dorsal area (n=10), then euthanized after either 7 or 30 days, and inflammation was evaluated according to an inflammatory cells score. <strong>Results</strong>: In the alveolar 7-day group, control group presented an inflammation score 1, while all other groups presented a score 2, except AH plus^® total mix group (3). After 30 days, all groups presented a score 1. The edemogenic test showed less edema in Sealapex^® groups (p &lt; 0.5). In subcutaneous 7-day period, all groups presented score 2. In 30 days, all groups revealed score 1, except AH Plus^® partial mix group (2). <strong>Conclusion: </strong>Regarding mixing of the sealers, there were no significant differences among the groups.</p><p><strong>Keywords</strong></p><p>AH Plus; Inflammation; Materials testing; Root canal filling materials; Sealapex.</p>