The aim of this study was to evaluate the subcutaneous connective tissue response of isogenic mice after implantation of different glass ionomer-based cements (EQUIA® Forte Fil, EQUIA® Fil and Ketac™ Universal Aplicap™). Eighty-seven isogenic BALB/c mice were allocated in 12 groups, 9 were considered as experimental groups (Ketac, E. Fil and E. Forte at 7, 21 and 63 days) and 3 controls (empty polyethylene tubes at 7, 21 and 63 days). After the experimental periods, the subcutaneous connective tissue surrounding the implanted material was removed and subjected to histotechnical processing and staining with hematoxylin and eosin. A histopathological description of the tissue reaction surrounding each material and a semi-quantitative analysis of collagen fiber formation and inflammatory infiltrate were performed. Additionally, the thickness of the granulomatous tissue in contact with each material was measured. Data were analyzed statistically (α=0.05) by the Kruskal-Wallis test, followed by Dunn post-test. Initially, the collagen fiber formation was not different among all the tested materials (p>0.05) but was different at 21 days with the control group presenting the most advanced stage of collagen fiber formation. At 63 days, EQUIA® Forte Fil group showed the most advanced stage of collagen fiber formation, compared to EQUIA® Fil group (p<0.05). The inflammatory infiltrate was not different among the tested materials in any experimental period (p>0.05). The thickness of the granulomatous tissue was greater in the E. Forte group, compared to control in all periods. All glass ionomer-based cements showed tissue compatibility, according to the evaluated parameters.