In the present study, the possible mechanisms by which interferon (IFN)-γ affects pregnancy were investigated using the cytokine network model. The IFN-γ-induced expression of interleukin (IL)-1β was examined using western blotting, immunohistochemistry and immunofluorescence. The results showed that IFN-γ treatment significantly decreased the expression of uterine IL-1β protein during the preimplantation, post-implantation and mid-gestation periods. The expression of IL-1β protein was increased after IFN-γ treatment compared with the control group in late pregnancy. In the placenta, IL-1β protein levels were significantly increased after IFN-γ treatment in early and mid-pregnancy. In late pregnancy, IFN-γ treatment significantly decreased placental IL-1β protein levels. IL-1β was mainly expressed in the myometrium, uterine arteries, decidua basalis, trophospongium of the junctional layer and trophoblastic epithelium of the labyrinthine layers. IL-1β was mainly located in the cytoplasm of in vitro cultured endometrial stromal cells (ESCs). IFN-γ treatment did not affect the distribution of IL-1β, only the expression of IL-1β. The effects of IFN-γ on the proliferation of ESCs were determined using an MTS (a novel tetrazolium compound) assay. IFN-γ treatment inhibited the proliferation of ESCs and decreased the weight of the fetus and placenta. These results indicate that exogenous IFN-γ affects the expression of IL-1β and inhibits ESC proliferation.