In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue or/and dexamethason were investigated. The results revealed that plasma nitric oxide levels were elevated at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexamethasone was found to blunt hypoglycemia and hyperlacticemia, to reduce the occurrence rate of loss of response to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to decrease the 24 h mortality. The results suggested that nitric oxide play an important role during the course of fatal P. aeruginosa sepsis, but it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.