To explain the relationship between low density lipoprotein(LDL) and local anticoagulation in the atherosclerotic pathogenesis, the effect of varied LDL concentration with different incubation time on the activation of protein C by thrombomodulin (TM) of the surface of cultured newborn bovine aortic endothelial cells was investigated. After incubation, thrombin, protein C, and S-2238 were used for measuring TM-dependent protein C activation. The results showed a significant decline of TM activity after incubation with over 6 mg·L-1 of LDL and a significantly negative correlation between the LDL concentration and TM activity (y=-0. 25x + 65.96, r=-0. 87, n= 175, p<0. 001 ). The longer the incubation time with more than 50 mg·L-1 of LDL was taken, the more significant inhibition of TM activity would be shown. Reaction rate of activated protein C generation was decreased in early, and increased later.These data suggest that elevated blood levels of LDL may contribute to the atherosclerotic pathogenesis by decreasig function of local anticoagulation.