Vascular endothelial dysfunction which is associated with increased oxidative stress and decreased endothelial-derived nitric oxide has been considered as a major initial event in various diseases, such as atherosclerosis, diabetes and ischemia/reperfusion (I/R) injury.  Previously we found that a broad-spectrum protein kinase C (PKC) inhibitor (i.e., Gö 6983) and a specific PKC beta II peptide inhibitor (PKC βII-) were cardioprotective in myocardial I/R injury.  However, the direct effects of Gö 6983 or PKC βII- on vascular endothelial dysfunction and the related leukocyte-endothelial interactions are still unclear.  The leukocyte rolling, adherence and transmigration were estimated by using intravital microscopy in rat mesenteric postcapillary venules.  We found that superfusion of N^G -nitro-L-arginine-methyl-ester (L-NAME, 50 µM) induced endothelial dysfunction and significantly increased leukocyte-endothelial interactions within a 2 hour period compared to Krebs’ buffer control group (P<0.05).  By contrast, Gö 6983 (25 nM-200 nM) or PKC βII- (0.1 µM-10 µM) dose-dependently attenuated these interactions induced by L-NAME (P<0.05).  Moreover, histological evaluation of Gö 6983 (200 nM) or PKC βII- (10 µM) superfused mesenteric tissue exhibited significantly less leukocyte adherence and tissue transmigration, as well as significantly less intercellular adhesion molecule-1 expression compared to L-NAME group.  Finally, in a rat extracorporeal shock wave lithotripsy model, we demonstrated that PKC βII- (0.055-0.55 mg/kg) significantly decreased oxidative stress when hydrogen peroxide was measured directly from rat renal veins (P<0.05).  In summary, Gö 6983 or PKC βII- can decrease the proinflammatory responses in vascular endothelium and may provide a potential clinical treatment to prevent vascular endothelial dysfunction.