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Background Low molecular weight heparin (LMWH),as one of anticoagulant drugs,has been used for the treatment of chronic obstructive pulmonary disease (COPD) with prethrombotic state,but the specific use time is unclear.The aim of the study is to observe the effect of LMWH at two different periods of prethrombotic state in COPD in rats and to find the optimal time to use LMWH.Methods Forty Wistar rats were randomly divided into 4 groups:normal control,raised for 55 days without any treatment; COPD control without LMWH,cigarette inhalation plus intratracheal instillation of lipopolysaccharide and hypodermic injection of normal saline once a day for 10 days; COPD control given LMWH 150 U/kg subcutaneous injection,once a day for 10 days starting day 15 (LMWH-d15); COPD control given LMWH 150 U/kg subcutaneous injection,once a day for 10 days starting day 29 (LMWH-d29).Results Comparing LMWH-d15 with LMWH-d29,plasma viscosity,whole blood viscosity,von Willebrand factor,serum fibrinogen,plasminogen activator inhibitor-1 and fibrin D-dimer were each significantly reduced; but thrombin plasminogen activator increased significantly whilst arterial PO2 and PCO2 improved significantly.Conclusion The better time to use LMWH is the time when coagulation and fibrinolytic indices begin to change in COPD.