ObjectiveTo explore the effects of cytoskeleton depolymerizing agent and stabilizer on the clathrin/caveolae-mediated endocytosis, the expression of membrane vascular endothelial cadherin (VE-cad), and the vascular permeability by the transformation of cytoskeleton structure after lipopolysaccharide (LPS) treatment. MethodsCRL-2922 cells were used in the experiments. Indexes were tested at corresponding time point according to name of group, but in blank control group indexes could be tested at any time point. CRL-2922 cells were divided into blank control group, LPS-1 h group, and LPS-4 h group to observe cytoskeleton structure; CRL-2922 cells were divided into LPS-1 h group, Cyt D+LPS-1 h group, LPS-4 h group, and Jasp+LPS-4 h group to determine the expression of membrane VE-cad, and to determine the expression of its co-immunoprecipitation with clathrin and caveolin-1 (Cav1); besides, CRL-2922 cells were divided into blank control group, LPS-1 h group, Cyt D+LPS-1 h group, LPS-4 h group, and Jasp+LPS-4 h group to detect the cumulative infiltration rate. Results①The cytoskeleton showed a dynamic change after LPS treat-ment, the F-actin polymerized and stress fibers formed at 1 hour after LPS treatment, but depolymerized at 4 hours after LPS treatment. ②Compared with LPS-1 h group, the level of co-immunoprecipitation of VE-cad with clathrin in Cyt D+ LPS-1 h group decreased (P<0.05), the level of co-immunoprecipitation of VE-cad with Cav1 increased (P<0.05), and expression level of VE-cad in plasma membrane decreased (P<0.05); compared with LPS-4 h group, there was no significant difference in the level of co-immunoprecipitation of VE-cad with clathrin of Jasp+LPS-4 h group (P>0.05), but the level of co-immunoprecipitation of VE-cad with Cav1 decreased in Jasp+LPS-4 h group (P<0.05), and expression level of VE-cad in plasma membrane increased (P<0.05). ③Compared with blank control group, the cumulative infiltration rates of LPS-1 h group and LPS-4 h group were both higher (P<0.05); compared with LPS-1 h group, the cumulative infiltration rate of Cyt D+LPS-1 h group was higher (P<0.05); compared with LPS-4 h group, the cumulative infiltration rate of Jasp+LPS-4 h group was lower (P<0.05). ConclusionActin cytoskeleton shifts from polymerization to depoly-merization after LPS treatment, the structural change of actin cytoskeleton is an important reason for the transformation of VE-cad endocytosis pathway from clathrin-mediated to caveolae-mediated after LPS treatment.