Adiponectin is a cytokine secreted by adipocytes, whose plasma levels are decreased in obesity. Adiponectin has insulin-sensitizing, antiatherogenic, and antidiabetogenic effects. It has been shown that adiponectin may also exert antineoplastic activity through suppression of tumor proliferation and neoangiogenesis and through induction of apoptosis. Recently, low adiponectin serum concentration has been found in obesity-related malignancies, including endometrial cancer. In addition, the expression of adiponectin receptors (AdipoR1 and AdipoR2) has been documented in several human cancer tissues, but the expression has previously not been assessed in human endometrial cancer tissues. In this study, we analyzed the immunohistochemical expression of AdipoR1 and AdipoR2 in a series of surgically resected human endometrioid adenocarcinoma tissues from a total of 141 cases. Decreased AdipoR1 or AdipoR2 expression was significantly associated with histological higher grade (P=0.0026 and 0.0004, respectively). Decreased expression of AdipoR1 was associated with myometrial invasion and lymph node metastasis of endometrioid adenocarcinoma (P=0.0039 and P=0.0069, respectively). AdipoR1 and AdipoR2 immunoexpression was significantly associated with the expression of the progesterone receptor, although it was not significantly correlated with the expression of the estrogen receptor, Ki-67 or p53. Our present study raises the possibility that decreased expression of adiponectin receptors is implicated in the development, invasion, and metastasis of human endometrioid adenocarcinoma. Our findings, moreover, indicate that adiponectin receptors could be considered as therapeutic targets for endometrioid adenocarcinoma. In adiponectin receptor-positive endometrioid adenocarcinoma, we think adiponectin-based anticancer therapy is useful; however, in histological high-grade endometrioid adenocarcinoma, in which the expression levels of adiponectin receptors are relatively low, adiponectin therapy supported by adiponectin receptor induction is needed.