Developing new restorative materials should avoid damage to tissue structures. This study evaluated the biocompatibility of a commercial dental glass ionomer cement (GIC) mechanically reinforced with cellulose microfibers (GIC+CM) or cellulose nanocrystals (GIC+CN) by implantation of three test specimens in subcutaneous tissue in the dorsal region of 15 Rattus norvegicus albinus rats. Each rat received one specimen of each cement, resulting in the following groups (n=15): Group GIC (Control), Group GIC+CM and Group GIC+NC. After time intervals of 7, 30 and 60 days, the animals were sacrificed and the following aspects were histologically evaluated: type of inflammatory cells, fibroblasts, blood vessels, macrophages, giant cells, type of inflammatory reaction and capsule thickness (µm). These events were scored as (-) absent, (+) light, (++) moderate and (+++) intense. The results were statistically analyzed by Kruskal-Wallis test and Mann-Whitney post test. At 7 days, Group GIC+NC showed more favorable tissue repair because quantitatively there were more fibroblasts (p=0.022), fewer macrophages (p=0.008) and mononuclear cells (p=0.033). Polymorphonuclear neutrophils and giant cells were absent in all experimental periods. At 60 days, test specimens in Group GIC+NC were surrounded by a fibrous tissue capsule with reduced thickness (26.72±2.87 µm) in comparison with Group GIC+CM (41.21±3.98 µm) (p=0.025). In general, all biomaterials showed satisfactory biocompatibility, but glass ionomer cement modified with cellulose nanocrystals showed a more advanced tissue repair.