Previous studies have shown that dexamethasone (Dex) induces the expression of TGF-1 in androgen- independent prostate cancer (AIPC) both in vitro and in vivo. However, it is not clear whether Dex has a direct effect on the expression of TGF- receptors. In this study, using the androgen independent human prostate cancer cell line, PC-3 cells, we demonstrated that Dex increased the expression of TGF- receptor type II (TRII), but not TGF- receptor type I (TRI) in a time- and dose-dependent manner. The up-regulation of TRII expression by Dex was mediated by glucocorticoid receptor and occurred at the transcriptional level. Dex also enhanced TGF-1 signaling and increased the expression of cyclin-dependent kinase inhibitors (CKI) p15^INK4B (p15) and p27^KIP1 (p27), which are the target genes of TGF-1 and have been identified as inducers of cell cycle arrest at the G1 checkpoint. The antiproliferative effect of Dex was partially blocked by anti-TRII antibody, indicating that elevated TRII and TGF-1 signaling were involved in the antiproliferative effect of Dex. Since the TGF-1 pathway could not fully explain the antiproliferative effect of Dex, we further examined the effects of Dex on the transcriptional activity of nuclear factor-B (NF-B) and the expression of IL-6 and found that Dex suppressed the transcriptional activity of NF-B and IL-6 mRNA expression in PC-3 cells. These results demonstrated that glucocorticoid inhibited the proliferation of PC-3 cells not only through enhancing growth-inhibitory TGF-1 signaling, but also through suppressing transcriptional activities of NF-B.