Objective To evaluate whether the goal of loose blood glucose concentration can reduce the incidence of hypoglycemia and blood glucose variability in critically ill patients with diabetes mellitus. Methods A total of 156 patients with type 2 diabetes mellitus were treated with ICU in our hospital. Patients were randomly divided into two groups, each group of 78 patients.A group of patients underwent intensive glycemic control(intensive group, n=78), that is, when any time blood glucose concentration≥10 mmol/L, the patient was given insulin to control blood sugar within 6～10 mmol/L. The other group was treated with loose blood glucose control(loose group, n=78). That is, when any blood glucose concentration≥14 mmol/L, the blood glucose control in 10～14 mmol/L. Blood glucose variability was assessed by calculating the coefficient of variation for each patient. The incidence of hypoglycemia in both groups was compared with the prognosis of the patient. Plasma concentrations of inflammatory markers, plasma glucose turnover, and oxidative stress were used to assess safety. Results Compared with the intensive group, the variation coefficient of blood glucose ［(23.9±7.8)% vs.(33.3±13.9)%, P=0.009］was significantly decreased in the loose group. The incidence of absolute hypoglycemia, the incidence of hypoglycemia and the rate of recurrent hypoglycemia were significantly lower in all patients(all P＜0.05). There was no significant difference between the two groups(P＞0.05)in the levels of Interleukin-6, high-sensitivity C-reactive protein, 1,5-anhydroglucitol and isoamectin(all P＞0.05). There was no significant difference in ICU mortality, hospital mortality and one-year mortalitybetween the two groups(P=0.197, 0.853 and 0.500). Conclusion Relaxed blood glucose control in patients with type 2 diabetes can reduce blood glucose variability and reduce the prevalence of hypoglycemia.