Objective To investigate the protective effects of penehyclidine hvdrochloride (PHC)on lipopolysaccharide ( LPS)-induced human umbilical vein endothelial cells (HUVECs) injury and the underlying mechanism.Methods Cultured HUVECs were divided into five groups:control group,LPS group,LPS/PHC ( 10 μg/L) group,LPS/PHC (25 μg/L) group,LPS/PHC (50 μg/L) group.Cell viability was measured by methyl thiazol tetrazolium (MTT) colorimetric method.The concentrations of lactate dehydrogenase (LDH) and nitric oxide (NO) were measured respectively by using chemical colorimetric method and nitrate reduction method.The expression of inducible nitric oxide synthase (iNOS) mRNA and protein was detected hy using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting respectively.The activity of nuclear factor-KB (NF-KB) and signal transducer and activators of transcription 3 (STAT3) were measured by enzyme linked immunosorbent assay (ELISA).Results As compared with control group,cell viability [(60.31 ± 8.76 )% vs 100.00%] was decreased and the concentrations of LDH [(326 ±52) μmol/L vs ( 125 ±25) μmoL/L] and NO [(55.49 ± 10.16) μmol/L vs ( 12.13 ±11.02) μmol/L] were increased in LPS group ( P <0.01 ) ; PHC could revere these effects on HUVECs (P <0.05).At the same time,PHC reduced the expression of iNOS mRNA and protein,and the activity of NF-KB and STAT3 ( P < 0.05 ).Conclusion PHC can protect the endothelial function by reducing the concentration of NO.Inhibiting the NF-KB and STAT3 signal pathway may be the underlying mechanism. Key words: Penehyclidine hydrochloride; Lipopolysaccharide; Human umbilical vein endothelial cells; Inducible nitric oxide synthase; Nitric oxide