The aim of this double-blind randomized study was to evaluate the biocompatibility of resin-modified glass ionomer cements (RMGIC) by means of morphological and immunohistochemical analyses. RMGICs were selected and divided into four groups: Group CK (Crosslink Orthodontic Band Cement); Group RS (Resilience Light Cure Band Cement) Group RMO (RMO Band Cement), Group TP (Transbond Plus Light Cure Band), and Group C (Control-polyethylene). The materials were implanted in rat subcutaneous tissues, randomly selected for this study. After time intervals of 7, 15, and 30 days the tissues were submitted to morphological analysis. In immunohistochemical analysis, the immuno-marking of antibody CD68 was evaluated. The results obtained were statistically analyzed by the Kruskal-Wallis and Dunn tests (p < .05). In the morphological analysis after 7 days, Groups RS, RMO and TP showed more intense inflammatory infiltrate (p = .004) and only Group RMO presented greater intensity of multinucleated giant cells (p = .027). In the immunohistochemical analysis, Groups RMO and RS were observed to present a larger quantity of CD68+ (p = .004) in the time interval of 7 days and only Group RMO presented statistically significant difference for this parameter after 15 days (p = .026). In the time interval of 30 days, Group RMO presented the largest quantity of multinucleated giant cells (p < .004). The RMGICS Crosslink and Transbond Plus provided significantly better tissue biocompatibility than the Resilience and RMO Cements.