Recent studies suggested that Ob (Ob) and its receptor (ObR) could be involved in the pathogenesis of various human malignancies, among others in endometrial cancer. Moreover, hypoxia, which is associated with solid tumors, might stimulate, through hypoxia-inducible factor 1alpha (HIF-1alpha), expression of Ob and ObR. In this article, we analyzed by immunohistochemistry the expression of Ob, ObR, and HIF-1alpha in 60 cases of human endometrial cancer tissues as well as in 25 cases of normal endometria. Additionally, we assessed correlations among studied proteins as well as relationships with selected clinicopathological features of endometrial cancer. Immunoreactivity for Ob, ObR, and HIF-1alpha protein was observed in 56.7%, 30.0%, and 78.3% of endometrial cancers, respectively. The expression of HIF-1alpha showed a significant positive correlation with Ob (P < 0.0001, r = 0.573) and ObR (P = 0.020, r = 0.299). Moreover, we noted positive correlation between Ob and ObR (P = 0.001, r = 0.429). No statistically significant relationship was revealed between Ob, ObR, and HIF-1alpha protein in regard to patient's age, histological grade, and extent of tumor growth (pT). In conclusion, HIF-1alpha, which is related to tissue hypoxia in endometrial cancer, seems to be associated with overexpression of Ob and ObR. Ob could exert autocrine effect to stimulate endometrial cancer progression. Thus the autocrine Ob loop should be taken into consideration as a novel potential target in endometrial cancer prevention and treatment.