Introduction The biocompatibility of chelating agents and organic acids have been explained by a variety of methods, and suggestions for use have been based more on clinical observations and physicochemical properties than on biological aspects. The present study aimed to evaluate the inflammatory response of 17% EDTA, 17% EDTA-T, and 10% citric acid in bony defect created in rat jaws. Methods Mandibular through and through critical size defects were created bilaterally in 60 rats. Fibrinol (Baldacchi SA, São Paulo, Brazil), a cube-shaped compound of absorbable bovine fibrin foam and sodium chloride, was used as a carrier of the substances. One side had received Fibrinol (control), whereas the opposite side had received Fibrinol soaked with each substance on the 1st, on the 7th, on the 14 th, and on the 28th day ( n = 5 for each day). Hemijaws were prepared for light microscopy, and samples were stained with hematoxylin and eosin. Digitized images were analyzed with a morphometric software (ImageJ; National Institute of Mental Health, Bethesda, MD). to obtain the number of inflammatory cells per area. Comparisons were performed by using the Kruskal-Wallis test ( p = 0.05). Results For all days, 10% citric acid and 17% EDTA-T showed, respectively, the lowest and highest number of inflammatory cells per area. All tested substances and controls showed the highest inflammatory cell response on the 14th day. Conclusion Among the tested substances, 10% citric acid proved to be the less aggressive tested solution at 14 days. At 28 days, all solutions were similar, but EDTA-T kept showing the higher number of inflammatory cells.