ObjectivesTo investigate immune intervention of 1,25-dihydroxyvitamin D3 on typeⅠdiabetes in streptozotocin-induced C57BL/6J mice and its possible mechanism.Methods1. Animal models: The diabetic animal model in C57BL/6J mice was established by intraperitoneal injection of streptozotocin (40mg·kg-1) i.p. for 5 consecutive days. The mice are considered diabetic when sequential blood glucose level is equal to or above 16.7mmol/L.2. Groups: (1) Control group: Normal mice were intraperitoneally injected with peanut oil once in two days for 7 times in the same volume as 1,25-dihydroxyvitamin D3 group.(2) Model group: The established diabetic mice instead of normal ones were handled with the same treatment in control group. (3)1,25-dihydroxyvitamin D3 group: diabetic C57BL/6J mice were treated with 1,25-dihydroxyvitamin D3(5μg·kg-1)i.p. every other day for 7 times totally.3. Blood glucose level was monitored using a one-touch blood glucose meter.4. Flow cytometry method was used to analyze Th1/Th2, CD4 CD25 Treg cells, and ELISA was employed to measure IL-10, IL-12 level.5. Cell morphological changes of pancreas, spleen, and kidney were monitored by optical and electron microscopy.6. The expression of cell apoptosis-related proteins including Bcl-2 and Beclin-1, and vitamin D receptor was investigated by immunohistochemical technique.Experimental results:1. Water consumption of 1,25-(OH)_2D_3 group is less than that of model group. However, there is no statistic difference in weight, food consumption, and blood glucose level.2. 1,25-(OH)_2D_3 can significantly increase Th1, CD4 CD25 Treg and IL-10 expression but suppress Th2 and IL-12 expression.3. In comparison with model group, inflammation level of pancreas, spleen, kidney cells in 1,25-(OH)_2D_3 group is significantly reduced.4. 1,25-(OH)_2D_3 can down-regulate the expression of Beclin-1 gene, which plays an important role in induction of cell autophagy. At the same time, it also induces up-regulation of apoptosis-inhibitory Bel-2 gene expression and vitamin D receptor expression.Conclusion:1,25-(OH)_2D_3 can obviously reduce pathological changes of pancreas, spleen, kidney cells in diabetic model mice. Its possible mechanisms include up-regulation of Th1, CD4~ CD25~ T_(reg), IL-10, and Bel-2 expression; down-regulation of Th2, IL-12 and Beclin-1 expression; as well as prevention of macrophage invasion.