OBJECTIVE To investigate the effects of immunosuppressive agents on insulin secretion of human islet cells in vitro. METHODS Human islet cells were isolated by the solution of the liberase and purified by Ficoll's density gradient centrifugation and then were exposed to various concentrations of four immunosuppressive agents for 24 hr respectively. Glucose-stimulated insulin secretion during subsequent static incubation was measured using the human insulin ELISA kit. RESULTS Glucose-stimulated insulin secretion from human islet cells was significantly reduced after exposed to high concentrations of MMF and FK506 (both P < 0.05). No significant reduction in insulin secretion was observed from human islet cells after exposed to FTY720 and rapamycin (both P > 0.05). CONCLUSIONS (1) High concentrations of MMF and FK506 have deleterious effects on insulin secretion in human islet cells. Low-dose FK506 + MMF is available for clinical use. (2) FTY720 and rapamycin have no adverse effects on insulin secretion in human islet cells. FTY720 and rapamycin may become useful immunosupressants for future clinical islet allotransplantation.