During rat pregnancy, some of the foetoplacental units undergo complete spontaneous resorption while the adjacent units remain unaffected. In an attempt to clarify the mechanisms implicated in this spontaneous resorption, implantation units from days 14 and 16 of pregnancy were examined. The number of implantation sites and resorption units was recorded, and uterine paraffin sections were stained with haematoxylin and eosin for the evaluation of tissue morphology. The incidence of resorption was about 9.2 % on day 14 and 8.2 % on day 16. Perforin and active caspase-3 immunostaining were performed for localization and characterization of uterine natural killer (uNK) and apoptotic cells, respectively. The α2-macroglobulin (α2-MG) expression was examined by in situ hybridization, immunohistochemistry and its levels quantified by enzyme-linked immunosorbent assay. A reduction in α2-MG decidual levels in resorpted units was observed when compared to normal implantation units in both days. This potent protease inhibitor is the major product secreted by the mesometrial decidual tissue and may constitute an indicator of maternal tissues remodelling abnormalities. Besides the decreased α2-MG levels, an increase in uNK cell number was found in resorption units. The decreased α2-MG levels may be related to the aberrant control of trophoblast invasion that may activate uNK cells. The elucidation of the mechanisms underlying natural pregnancy loss in rat may contribute for the clarification of the "vanishing twin" phenomenon that occurs in human pregnancy.