Glomerular endothelial cell (GEC) injuries plays a huge role in early stage of diabetic nephropathy (DN). Previous research has shown that the PKC|? inhibitor works well for the treatment of DN. In the present study we further explored the results and molecular mechanisms of PKC|? inhibitors on GEC apoptosis in DN in streptozotocin-caused diabetic rodents in vivo and glucose- or PMA-treated human kidney glomerular endothelial cells (HRGECs) in vitro. Within the diabetic rodents, hyperglycemia caused irritated nephropathy and GEC apoptosis supported by considerably elevated expression of swiprosin-1, a potentally pro-apoptotic protein. Administration of LY333531 (1 mg?¡èkg-1?¡èd-1 for 8 days) considerably attenuated both GEC apoptosis and swiprosin-1 upregulation within the diabetic rodents. Similar outcome was noticed in high glucose- or PMA-treated HRGECs in vitro. The professional-apoptotic role of swiprosin-1 was further examined using HRGECs given lentivirus mediating RNA interference or higher-expression and swiprosin-1-knockout rodents. Over-expression of swiprosin-one in HRGECs led to increases in apoptosis as well as in caspase-9, caspase-3 and Bax expression. In comparison, knockdown of swiprosin-1 attenuated high glucose- or PMA-caused HRGECs apoptosis. In addition, over-expression of swiprosin-1 promoted interaction between swiprosin-1 and caspase-9 and elevated the development of apoptosomes. In diabetic swiprosin-1-/- rodents, the kidney/bodyweight, urinary albumin, glomerular hypertrophy, mitochondrial apoptotic-connected proteins and GEC apoptosis were considerably attenuated compared to individuals in diabetic swiprosin-1 / rodents. These results show swiprosin-1 expires-controlled by PKC|? in early stage of DN, which PKC|? facilitates GEC apoptosis with the mitochondrial-dependent path.