Objective To observe the clinical efficacy of low-molecular-weight heparin calcium combined with aerosol inhalation of salbutamol and non-invasive positive pressure ventilation (NIPPV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease with type II respiratory failure. Methods From January 2016 to January 2021，90 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with type II respiratory failure treated in the Department of Respiratory Medicine，Affiliated Hospital of Southwest Medical University were selected as the research subjects. According to the treatment methods，patients were divided into control group and experimental group，with 45 cases in each group. Patients in control group were treated with salbutamol inhalation and NIPPV on the basis of conventional treatment，while the experimental group was treated with low-molecular-weight heparin calcium on the basis of control group，and the two groups were treated continuously for one cycle (14 days).The changes of blood routine，arterial blood gas analysis，lung function，coagulation function indexes，PASP，ET-1，hs-CRP，NT-proBNP，as well as the time of non-invasive mechanical ventilation，the total length of hospitalization and the occurrence of adverse reactions were compared between the two groups before and after treatment. Results (1) There was no significant difference in HCT，Hb，PLT and RBC before treatment in the control group (P > 0.05). After treatment，the levels of control group were lower than that of experimental group，with statistically significant differences (P < 0.05). (2) Comparing PaO2，PaCO2，pH and SaO2 between the two groups ，there were no statistically significant differences before treatment (P > 0.05).After treatment

PaO2，pH and SaO2 of the experimental group were higher than the control group ，and PaCO2 was lower than the control group

with statistically significant differences(P < 0.05).(3) Comparing the FEV1/FVC and PEF between the two groups，the results showed that the difference before treatment was not statistically significant (P > 0.05)； after treatment，the FEV1/FVC and the PEF of the control group were higher than these of the experimental group (P ＜0.05).(4) The ATPP，PT，TT，Fib and D-D values of the two groups were compared，and there were no significant differences before treatment (P > 0.05). After treatment，the levels of ATPP，PT，TT，Fib and D-D in experimental group were lower than those in control group，and the differences were statistically significant (P < 0.05). (5) The levels of hs-CRP，PASP，NT-proBNP and ET-1were compared，there were no significant differences before treatment (P > 0.05)，but after treatment，the values of experimental group were lower than control group，and the differences were statistically significant (P < 0.05).(6) The duration of non-invasive mechanical ventilation and hospital stay in the control group were shorter than those in the experimental group (P＜0.05).(7) Comparing the incidence of adverse reactions among patients，the difference was not statistically significant （P > 0.05). Conclusion Low-molecular-weight heparin calcium combined with aerosol inhalation of salbutamol and non-invasive positive pressure ventilation in the treatment of acute exacerbation of chronic obstructive pulmonary disease with type 2 respiratory failure has definite curative effect，high safety，and can be promoted for clinical treatment.