Phosphoinositide3-kinase (PI3K) is involved in regulation of many kinds of physiological processes in cells, such as vesicle transportation, cytoskeleton reorganization, cell survival, phagocytosis, apoptosis, and so on. It is an important regulator of vesicle edocytosis. According to preview reports, PI3K seems to be one of regulators of cell secretion. To inspect this, the effect of PI3K on PC12 cell secretion was checked by using its specific inhibitor wortmannin. Wortmannin inhibited PI3K activity indicated by loss of EGFP-2xFYVE fusion protein binding to the PtdIns-3-P which is localized in early endosome, and did not change PC12 cell response to flash including its kinetics and calcium dependence. The result demonstrated that PI3K has no effect on PC12 cell secretion itself, but does not exclude the possibility that it enhances cell to response to repetitive strong stimuli by its accelerating effect on vesicle endocytosis which speeds up the refilling of releasable vesicle.