Objective To observe the effects of penehyclidine hydrochloride ( PHCD) combined with mechanical ventilation ( MV) on inflammatory response in rats with ARDS induced by oleic acid ( OA) .Methods The rat ARDS model was established by OA via intravenous injection ( iv) . 32 adult healthy male SD rats were randomly divided into four groups, ie. a normal control group( group C: intra-peritoneal injection of a same amount of normal saline and intravenous injection of a same amount of normal saline respectively rather than PHCD) , a model group( group A1) , a PHCD group ( group A2: intra-peritoneal injection of 0. 5 mg/kg PHCD30 minutes before OA iv) and a PHCD+MV group ( group A3: VT = 4 mL/kg,respiratory rate =70 beats /min, I∶E =1∶2, FiO2 =21%) . Four hours after OA iv, arterial partial pressure of oxygen ( PaO2 ) was measured, and the oxygenation index ( PaO2 /FiO2 ) as well as wet /dry weight ratio( W/D) of lung tissue were calculated respectively. The pathological changes of lung tissue was observed through light microspcope. Interlukin-8 ( IL-8 ) , myeloperoxidase ( MPO) and NF-κB in lung tissue homogenate were measured by enzyme linked immunosorbent assay ( ELISA ) . Results Extensive pneumonedema, pneumorrhagia, focal atelectasis and amout of inflammatory cells infiltration in lung tissues were all revealed in ARDS rats. Lung injury score ( 8. 63 ±2. 20 vs. 1. 38 ±0. 92) , W/D ratio ( 8. 37 ±0. 99 vs. 4. 08 ±0. 65) were all higher in the ARDS rats than those in group C( all P lt;0. 01) . PaO2 /FiO2 was lower in group A1 than that in group C [ ( 206 ±32) mm Hg vs. ( 428 ±28) mm Hg, P lt; 0. 01] . The concentrations of MPO [ ( 33. 91 ±1. 43) ng/mL vs. ( 20. 92 ±1. 40) ng/mL) ] , IL-8 [ ( 809 ±39) ng/L vs. ( 583 ±91) ng/L] and NF-κB [ ( 1163 ±105) ng/L vs. ( 803 ±130) ng/L] in lung tissue homogenate were significantly increased in the ARDS rats than those in group C ( all P lt;0. 01) . Pathological changes of lung tissue ( including pneumonedema, pneumorrhagia, atelectasis and inflammatory cell infiltration, etc. )obviously improved when treated by PHCD or/and PHCD combined with MV ( all P lt;0. 05) . PaO2 /FiO2 in group A2 and A3 were both significantly increased when compared with group A1 ( both P lt; 0. 05) .Meanwhile,W/D ratio, lung injury score, and concentrations of MOP, IL-8 and NF-κB were sharply decreased in group A2 and A3 ( all P lt;0. 05) . The improvement in all above indices were more significant in group A3 than those in group A2, despite all those indices failed to meet the levels of normal rats ( all P lt; 0. 05) .Conclusion PHCD can inhibit the inflammatory response in ARDS rats induced by OA iv, through which it protect the lung tissue frominjury induced by OA. The protective role of PHCD plus MV is superior to that of PHCD only.