Objective:To investigate the effect of nebulized Ketamine inhalation and i.p. injection on oxidative stress in the lungs of asthmatic rats. Methods:Fifty-one Brown Norway rats(were randomly assigned to seven groups,which were control group(C) with 7 rats,asthma group(A) with 8 rats,Ketamine inhaled groups(K1,K2,K3) each with 8 rats,and Ketamine i.p. injected groups(V1-V2) each with 6 rats. In group A,K1,K2,K3,V1,V2,asthma was induced by two steps:The rats were received subcutaneous injection of ovalbumia and aluminum hydroxide in PBS,and then inhaled nebulized 1% OVA in PBS. In group K1,K2 and K3,the sensitized rats were exposed to 12.5 mg/ml(K1 group),25.0 mg/ml(K2 group),50.0 mg/ml(K3 group)of nebulized Ketamine before inhaling nebulized OVA. In groupV1 and V2,the sensitized rats were i.p. injected with 50 μg/kg ketamine(V1) and 100 μg/kg(V2) before inhaling nebulized OVA. Lung samples were taken and made into tissue bomogenate,and the protein were extracted. ROS were measured with kit,and p38 was detected by Western-blot. Results:The ability of anti OH· and O2·- of group A was lower than group K1-K2 and V1(P < 0.01)and K3-V2(P < 0.05). The activity of SOD of group A was lower than group K1-K2 and V1(P < 0.01) and K3-V2(P < 0.05). Compared with group C,the ability of anti-oxidative stress of group A was significantly decreased(P < 0.01). Compared with group C,the activation of p38 of group A was significantly increased(P < 0.01),also the activation of p38 in group A was higher than group K1-K2 and V1(P < 0.01) and K3-V2(P < 0.05). Conclusion:Inhalation of nebulized Ketamine and i.p. injected with Ketamine can restrain the oxidative stress reaction and the activation of p38 in lung in asthmatic rats. 12.5 mg/ml nebulized ketamine and 50.0 μg/kg i.p. injected with Ketamine appears to be enough for satisfactory clinical results.