Objective:To investigate the effect of hydrogen sulfide on the neurogenic inflammation in mouse lung tissues ,and its mechanism .Methods:Eight‐week old ,male Balb/c mice were randomly divided into the following groups:control group , NaHS group ,CP‐96345 + NaHS group、capsaicin + NaHS group and capsazepine + NaHS group .The mice were pretreated with vehicle ,CP‐96345 (2 .5 mg/kg ,i .p .) ,capsaicin (50 mg/kg ,s .c .) or capsazepine (15 mg/kg ,s .c .) and then received NaHS (10 mg/kg ,i .p .) or 0 .9% NaCl solution .One hour after intervention ,the mice were sacrificed ,then the concentration of substance P in plasma and the levels of tumor necrosis factor‐alpha (TNF‐α) and interleukine‐1 beta (IL‐1β) in lung homoge‐nate were measured by ELISA assay .Myeloperoxidase (MPO) activity in lung tissues was detected by tetramethyl benzidine (TMB) .The pathological changes of lung tissues were stained with hematoxylin and eosin .On the other hand ,the prepro‐tachykinin‐A (PPT‐A) gene knockout mice (eight‐week old ,female ,PPT‐A‐/‐) and their corresponding wild‐type Balb/c mice (eight‐week old ,female ,PPT‐A+ /+ ) were randomly given 0 .9% NaCl solution or NaHS (10 mg/kg ,i .p .) .One hour after intervention ,the mice were sacrificed ,then MPO activity ,TNF‐α and IL‐1β levels in lung tissues as well as the pathological changes of lung tissues were examined .Results:Hydrogen sulfide donor drug NaHS elevated significantly plasma substance P concentration (P<0 .05) ,lung MPO activity as well as lung TNF‐αand IL‐1βlevels (all P<0 .05) ,resulting in lung inflam‐matory injury .The knockout of PPT‐A gene ,or pretreatment with CP‐96345 ,capsaicin or capsazepine abolished significantly the elevation of lung MPO activity ,lung TNF‐αand IL‐1βlevels ,as well as the lung injury induced by NaHS (all P<0 .05) . Conclusions :Hydrogen sulfide may induce lung inflammatory injury through stimulating the release of substance P in nerve end‐ing s .