1,25(OH)(2)D-3, the active metabolite of vitamin D-3, its activity is not limited to mineral and skeletal homeostasis. In recent years, there has been increasing evidence pointing to the role of its activity in the regulation of cell proliferation, cell differentiation and immunomodulation. Here we report lipopolysaccharide (LPS), a glycolipid that is produced and secreted by gram-negative bacteria during peritonitis, plus high glucose (HG) can significantly inhibit mesothelial cell viability while induce more apoptosis in rat peritoneal mesothelial cells (RPMC). Pretreatment with 1,25(OH)(2)D-3 can reverse the above effect in a concentration dependent manner. HG plus LPS can down-regulate the levels of both mRNA and protein of VDR, and up-regulate the expression of TGF-beta 1 and TNF-alpha in RPMC, which can also be effectively reversed by pretreatment with 1,25(OH)(2)D-3. The above results suggest that HG plus LPS may induce changes in RPMC's viability and apoptosis, leading to peritoneal injury. 1,25(OH)(2)D-3 can reverse the inhibition of cell viability, the increase of apoptotic rate and induction of fibrosis related cytokine TGF-beta 1 and TNF-alpha by HG plus LPS in RPMC, thus protect peritoneal membrane. (C) 2011 Elsevier Inc. All rights reserved.