Objective:To investigate the effect of 1,25(OH)2D3 on prevention of acute rejection model of F344-Lewis rat pancreas transplantation. Methods:Pancreatic allograft from F344 rats was transplanted to Lewis recipients. Group A(untreated allogeneic control),Group B(rapamycin treatment),Group C(1,25(OH)2D3 treatment),15 rats were in each.;The blood glucose in the recipients,the pathological changes of the allografts and the survival of pancreatic allografts were observed. And the recipients’ peripheral blood,spleens and grafts were harvested from recipient to determine the CD3+ CD8+ T cells,CD4+ T cells and CD4+CD25+ T by flow cytometry. After transplantation,the level of serum interferon-2,4,10,12 in the recipients was determined by ELISA kit analysis also. Dendritic Cells (DC) of Lewis were derived from bone marrow cells in the culture with 1,25(OH)2D3. The expression of CD80,CD86 and MHCⅡmolecules was assessed by flow cytometry. Results:1,25(OH)2D3 significantly inhibited acute rejection,protected allografted function[blood glucose(5.12 ± 0.89) VS (12.41 ± 1.16)],and prolonged recipient survival. The population of CD8+T cell and CD4+T cell decreased in group B and C,though more CD4+CD25+ T cells were detected in group C. The differences in group C were apparent compared to A and B(P < 0.01). Concentration of Th1-type cytokine in serum decreased markedly,and Th2-type cytokine increased significantly. The mature of DCs was inhibited by 1,25(OH)2D3,and CD80,CD86,MHCⅡmolecules expression on the DC was significantly decreased in the presence of 1,25(OH)2D3. Conclusion:1,25(OH)2D3 could not only induce tolerogenic DCs but also might be enhance the number of CD4+CD25+ regulatory T cells. In such a way,the acute rejection might be inhibited, and the recipients survival might be prolonged.