Objective To investigate the effect of different blood glucose management under intensive insulin therapy on blood coagulation in patients with sepsis. Methods A randomized, prospective, double-blind, clinical intervention study was designed. In the First  Affiliated Hospital of Shihezi University from October 2015 to September 2016, 90 cases of sepsis patients were randomly divided into 3 groups according to the random number table method. The 30 cases were randomly divided into groups. Group A: control blood sugar 4.4~6.1 mmol/L, group B: control blood sugar 6.1~8.3 mmol/L, group C: control blood sugar 8.3~10.0 mmol/L. All patients after treatment in 1, 3, 7 days at different time points were monitored indexes of coagulation function, simultaneous recording of groups with gender, age, APACHE Ⅱ score, white blood cell count (WBC), treatment level of blood glucose, hypoglycemia incidence and the ICU hospitalization days, 28 days mortality. Results Three groups of patients before (T0) and after treatment of coagulation indicators, compared with the three groups before treatment, the difference was not statistically significant (P>0.05). There was significant difference between the group A and the group B, C, the difference was statistically significant (P<0.05). There was significant difference between group B and group C (P<0.05). Comparison of different monitoring time points was made in the same group. Three days and seven days after treatment in group A, APTT (s), PT (s), FIB(s), PLT(×109) were improved compared with those before treatment, and the difference was statistically significant (P<0.05). Seven days after treatment, APTT, PT, FIB, PLT in group B were improved compared with those before treatment, and the difference was statistically significant (P<0.05). There was no significant difference in group C (P>0.05). Seven days after treatment, D-dimer level in group A was significantly decreased compared with that before treatment (P<0.05), but the D-dimer levels in group B and group C were not significantly changed by the treatment (P>0.05). Conclusion In patients with sepsis, blood sugar control within 4.4~6.1 mmol/L, can significantly improve the coagulation function, the survival rate of 28 d and the prognosis.