Abstract: Objective To explore the high risk factors of adverse reactions such as hypoglycemia in patients with type 2 diabetes mellitus after initial insulin treatment, and to put forward suggestions on nursing measures. Methods The clinical data of 90 inpatients with type 2 diabetes mellitus who first used insulin in our hospital from January 2017 to June 2017 were retrospectively analyzed. The patients were divided into two groups according to the occurrence of hypoglycemia during the follow-up period of one year after discharge, and according to the occurrence of hypoglycemia, they were divided into two groups. The basic data, state-trait anxiety and insulin treatment knowledge questionnaire scores, biochemical indicators and oxidative stress indicators were collected to identify the high-risk factors for adverse reactions, and nursing intervention was given. The occurrence of hypoglycemia and changes of related indicators were observed after intervention. Results There were significant differences in body mass index, S-AI, T-AI, insulin treatment knowledge score, albumin, serum creatinine, triglyceride, fasting C-peptide, urinary protein, glycosylated hemoglobin and 8-carboxydeoxyguanosine levels between the two groups (all P<0.05). Body mass index, insulin therapy knowledge assessment and glycosylated hemoglobin content were independent protective factors for preventing hypoglycemic reaction, while serum creatinine level, urinary protein quantification and S-AI, T-AI were high risk factors for hypoglycemic reaction (all P<0.05); after targeted nursing intervention, the incidence of hypoglycemia in the observation group decreased from 39 cases to 10 cases (χ²=46.163, P<0.05). After intervention, the ST-AI of observation group was lower than that before intervention, while the score of insulin therapy knowledge questionnaire was higher than that before intervention (all P<0.05). Conclusion In the first intensive insulin therapy for type 2 diabetes mellitus, for type 2 diabetes mellitus patients with low body weight, low glycosylated hemoglobin content and initial insulin treatment, more attention should be paid to the knowledge of insulin use, trial teaching and the occurrence of hypoglycemic reaction after insulin treatment, so as to obtain better clinical prognosis.