〔Abstract〕 To investigate the effect of receptor of activated protein kinase C 1 ( RACK1) on lipopo- lysaccharide ( LPS) -induced barrier function in rat pulmonary microvascular endothelial cells ( RPMVEC) and its interplay with the Sonic hedgehog ( SHH) signaling pathway．Methods RPMVEC were cultured in vitro and ran- domly divided into si-NC，si-NC + LPS，si-RACK1，si-RACK1 + LPS，si-RACK1 + LPS + Vismodegib and Vis- modegib + SAG groups．The RACK1 of RPMVEC was silenced by small interfering RNA ( siRNA) technology and the cells were treated with LPS ( 10 mg / L) ，SHH signaling pathway inhibitor ( Vismodegib) ( 20 μmol / L) and SHH signaling pathway agonist ( SAG) ( 1 μmol / L) ．Following the intervention，the expressions of RACK1 and caveolin-1 in RPMVEC were detected by immunofluorescence ，while the transendothelial electrical resistance ( TEER) was evaluated using the method of Transwell，and the expression levels of RACK1，glioma-associated on- cogene homolog 1 ( Gli-1) and caveolin-1 were detected by Western blot．Results Silencing RACK1 increased the TEER value of RPMVEC induced by LPS ( P＜0. 05) ．The expression of caveolin-1 decreased ( P＜0. 05) ，and the expression of Gli-1 increased ( P ＜0. 05) ．Inhibiting the SHH signaling pathway could reverse the increased TEER value of LPS-induced RPMVEC caused by silencing RACK1 ( P ＜0. 05) ，and the expressions of RACK1 and caveolin-1 increased ( P＜0. 05) ．Activation of the SHH signaling pathway increased the TEER value of LPS- induced RPMVEC caused by silencing RACK1 ( P ＜0. 05) ，and the expressions of RACK1 and caveolin-1 de- creased ( P＜0. 05) ．Conclusion RACK1 plays a role in LPS-induced hyperpermeability of RPMVEC，and its effect may be achieved by modulating the SHH signaling pathway and caveolin-1．