Summary This study evaluates the effect of exogenous nitric oxide (NO), S-nitroso-N-acetyl-penicillamine (SNAP) on plasminogen activator inhibitor (PAI) activity and glomerular fibrin deposition in rats with experimentally induced endotoxemia. PAI activity increased in rats after Lipopolysaccharide (LPS) administration and in rats receiving a nitric oxide synthase inhibitor, N G-nitroso-L-arginine methyl ester (L-NAME). The combination of LPS and L-NAME further increase PAI activity as compared with LPS alone ( P<0.05). By contrast, the administration of SNAP to LPS rats reduced the increase in PAI activity and inhibited the additional increase in PAI activity induced by L-NAME. Plasma levels of plasminogen and antiplasmin were unchanged in all the studied groups. While rats receiving LPS+L-NAME developed glomerular thrombosis, the addition of SNAP significantly reduced fibrin deposition of the glomeruli ( P<0.01). This data suggests that NO affects the fibrinolytic system during endotoxemia by modulating PAI activity. Thus NO, to some degree, can protect against the procoagulant effect of LPS.