Introduction: The objective of this study was to determine the effects of chorioamnionitis on the extracellular matrix (ECM) structural glycoproteins of the developing human fetal spleen, and their influence on the haematopoiesis and spleen immune system compared to controls. Materials and Methods: After elective induced pregnancy termination due to chorioamnionitis or voluntary abortion, paraffin-embedded specimens from the spleen and respective fetal membranes of 90 fetuses were investigated by immunohistochemistry for presence of ECM structural glycoproteins, haematopoietic, and lymphoid cells. Conventional histological examination of the relative fetal membranes was performed. Results: The present results showed no quantitative variations in the expression of the ECM glycoproteins and haematopoietic lineages of the fetal spleen parenchyma at the end of first trimester (in both groups). At the second and third trimesters, acute chorioamnionitis showed a decreased number of the aforementioned proteins, with an increase of granulopoiesis and CD34 progenitor/stem haematopoietic cells. The immune system of the spleen during the third trimester demonstrated a decrease of both B and T lymphocytes, in comparison with controls. Conclusions: These results suggest that toxins and cytokines generated during chorioamnionitis, seem to influence ECM structural glycoproteins synthesis and release in fetal splenic parenchyma by reducing them, and probably cause further disorders of haematopoiesis and lymphopoiesis.