Abstract: Objective To examine the effect of tetraethylammonium (TEA, K~+ channel blocker) on pancreatic β-cell apoptosis and explore the mechanism. Methods Mouse β cells (NIT cells) were exposed to streptozotocin(STZ) to induce apoptosis, and TEA of different concentrations were applied along with STZ to prevent efflux of intracellular K~+. Cells were stained with annexin V, PI and rhodamine 123. Flow cytometer (FCM) was used to determine the percent of apoptotic or viable cells and the change of mitochondrial membrane potential. Culture media was collected to quantify the content of NO and ROS produced by NIT-cells. Cells were collected for detecting the activity of super oxide dismutase (SOD) in cells lysates. Results STZ induced apoptosis of NIT cells significantly (P<0.01) and 1 mmol/L TEA inhibited the effect of STZ (P<0.01). Productions of ROS (P<0.01)and NO (P<0.01) in NIT cells treated with STZ were reduced by TEA significantly. Activity of SOD in cytoplasm of NIT cells was down-regulated by STZ(P<0.01) significantly. Conclusions K~+ channel may play an important role in apoptosis of pancreatic β cells. K~+ channel blocker TEA may inhibit the apoptosis of pancreatic β cells significantly, which may correlate the down-regulating activity of SOD and the reducing of production of ROS and NO.