Objective To explore the efficacy of bi-level positive airway pressure ( BiPAP)ventilation plus plateau exhalation valve ( PEV) combined with respiratory stimulant for the treatment of pulmonary encephalopathy in patients with acute exacerbation of chronic obstructive pulmonary disease( AECOPD) . Methods 70 AECOPD patients with pulmonary encephalopathy were randomly divided into a control group and a treatment group. All patients received BiPAP ventilation and conventional therapyincluding antimicrobial, bronchodilation, and expectorant treatment. In the treatment group, the BiPAP ventilator was connected to PEV additionally, and naloxone and nikethamide were administered for 3 days.Clinical symptoms, blood gas analysis, vital signs, gas leakage conditions, and adverse reactions were recorded. Results Heart rate, respiratory rate, PaCO2 , and APACHEⅡ score were more significantly lower,the time to recover consciousness was shoter, meanwhile PaO2 , SaO2 , pH, and glasgow coma scale were significantly higher in the treatment group compared with the control group( all P lt; 0. 01) . Two cases in the treatment group and 5 cases in the control group received tracheal intubation and invasive ventilation due to treatment failure. Two elderly patients in the control group died in hospital. Conclusion Noninvasive positive pressure ventilation plus PEV combined with respiratory stimulant can significantly improve symptoms, shorten the time to recover consciousness, reduce the rate of endotracheal intubation, and improve hypoxemia and hypercapnia rapidly in AECOPD patients with pulmonary encephalopathy.