The biocompatibility of irrigant solutions, including 8.25% sodium hypochlorite (NaOCl), was analyzed in samples (n = 25) of chorioallantoic membranes (CAM) from embryos of the Gallus gallus, using the hen's egg test on chorioallantoic membrane (HET‐CAM). The following irrigants were tested: saline (control), 2% chlorhexidine (2% CHX), and NaOCl (2.5%, 5.25%, and 8.25%), and morphological and microcirculatory changes were investigated. Images were selected and quantified with Image J®. The macroscopic data were submitted to ANOVA, followed by the Tukey's test (p < .05); non‐parametric Kruskal‐Wallis and Mann–Whitney tests were applied to histological data (p < .05). The frequency of hyperemia differed significantly in the 8.25% NaOCl compared to the other groups, with the exception of 5.25% NaOCl (p = .096). Coagulation was more frequent in the 2% CHX group, differing significantly from the 2.5% NaOCl group (p = .038). In mean values, NaOCl 8.25% caused the decrease (NaOCl = 2.60, and control = 5.00) of vessels in the microcirculation, as well as triggered the increase (NaOCl = 425.50, and control 44.50) of inflammatory cells in the observed areas. There was necrosis in all samples in the 5.25% NaOCl group and in 80% in the 2% CHX, 2.5% NaOCl, and 8.25% NaOCl groups. Fibroblasts were detected only in the control group. It was concluded that the 8.25% NaOCl solution showed significantly high toxicity on CAM. However, these results were comparable to the other concentrations of NaOCl and to 2% CHX. Thus, in this experimental protocol, 8.25% NaOCl proved to be viable as an irrigant solution.