Abstract: OBJECTIVE To investigate the hypoglycemic action and β-cell protective effect of salidroside in streptozotocin（STZ） induced diabetic mice and cultured mouse islets. METHODS C57BL/6J mice were injected with a single dose of 150 mg/kg freshly prepared STZ with citrate buffer as control. The salidroside intervention with a dosage of 100 mg/kg/d was initiated on the 8th day after STZ injection and conducted for 30 d. Fasting blood glucose levels were measured every five days. After 30 d treatment， the oral glucose tolerance test(OGTT) was performed， and blood samples were collected to detect plasma insulin concentrations. The isolated mouse islets were cultured with salidroside(50 μmol/L) or DMSO for 3 d. Ki67 staining and TUNEL assay were performed to investigate the effects of salidroside on β-cell proliferation and apoptosis. Meanwhile， the mRNA levels of insulin，Pdx-1，GLP-1R and IL-1β in islets were detected by RT-PCR. RESULTS Compared with the STZ group， salidroside displayed significantly hypoglycemic effects， together with increased plasma insulin contents as well as improved OGTT. The Ki67 staining in cultured islets showed the proliferation of β-cell was remarkably increased by salidroside， while the β-cell apoptosis induced by high glucose was strongly inhibited by salidroside. Moreover， the mRNA levels of insulin， Pdx-1 and GLP-1R were up-regulated by salidroside significantly. However， the mRNA level of IL-1β which is a cytokine involved in β-cell apoptosis was down-regulated by salidroside. CONCLUSION The present study demonstrates that salidroside can ameliorate the hyperglycemia in STZ diabetic mice by protecting β-cell survival with increased β-cell proliferation and decreased β-cell apoptosis.