Abstract： Objective To investigate the effect of mild hypothermia therapy on plasma tissue-type plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) in patients with massive cerebral infarction (MCI).Methods The patients with MCI were randomly divided into the conventional therapy group and the mild hypothermia therapy group.On the basis of conventional therapy,the latter received local mild hypothermia therapy for 48 hours immediately after admission.Enzyme-linked immunosorbent assay was used to detect plasma tPA and PAI-1 at admission and at 48 hours after mild hypothermia,respectively.The general information and the tPA and PAI-1 levels before and after treatment in both groups were compared.Results A total of 46 patients with MCI were included.There were 26 and 20 patients in the conventional therapy group and the mild hypothermia therapy group,respectively.There were no significant differences in the general information,the tPA and PAI-1 levels before and after treatment in both groups,and the levels of plasma tPA (80.98 ± 34.64 pg/mL vs.110.1 ± 32.7 pg/mL; t =3.462,P =0.013) and PAI-1 (145.40 ± 45.29 pg/mL vs.174.2 ± 38.0 pg/mL; t =4.854,P =0.034) at 48 hours of mild hypothermia therapy in the mild hypothermia therapy group were significantly lower than those in the conventional therapy group.Conclusions Mild hypothermia therapy may decrease the plasma tPA and PAI-1 levels in patients with MCI,and it may be associated with the neuroprotective effect of hypothermia therapy.