Objective To investigate the toxic effects of rapamycin and its derivatives, everolimus, cefotiam, zotarolimus on islets. Methods Experiments were performed on mouse insulinoma cells（MIN6）cells. MIN6 cells were cultured in a medium containing everolimus, diphospholimus, and zotarolimus for 48 hours, and cell proliferation was detected by Brdu. Cell viability was detected by CCK8, cell cycle was detected by PI, cell apoptosis was detected by flow cytometry, and insulin secretion by cells was detected by ELISA. The effects of three rapamycin derivatives on MIN6 cells were observed. Results We found that rapamycin derivatives impaired cell proliferation and viability. In the cell cycle and apoptosis experiments, the effect of three derivatives on MIN6 cells compared with the negative control, showed the trend of inhibited G1 phase to S phase transition and promoted apoptosis，but the difference had not statistically significant. So did Apotosis experiment. Morever，rapamycin derivatives treatment of MIN6 cells resulted in a loss of cell insulin secretion，the difference had statistically significant. Conclusion This report provides evidence that rapamycin derivatives ，as the same as the rapamycin ，had toxicity to islets.