To examine the changes in P38MAPK during and after cardiopulmonary bypass (CPB) and the effect of SB203580, a specific P38MAPK inhibitor, on CPB-induced pulmonary inflammatory response.Fifty-four SD rats were randomized into 3 groups (each=18), namely sham CPB group, CPB group, and SB203580 group in which rats underwent CPB with SB203580 pretreatment. The lungs were excised immediately after the rats were sacrificed at scheduled time points and p38, nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were detected.The activities of P38 MAPK and NF-kappaB were significantly increased in CPB group as compared with those in sham CPB group. CPB resulted in increased TNF-alpha and IL-1beta production in the lung tissues. Administration of SB203580 prevented up-regulation of lung phosphorylated P38 MAPK, and decreased proinflammatory cytokine productions in the lung tissues.P38 MAPK is activated in the lung tissue during and after CPB to affect the activation of NF-kappaB in the lung; SB203580 selectively inhibits P38 MAPK activation to reduce proinflammatory cytokine production after CPB.