Abstract：Objective：To observe the efficacy of berberine combined with Mecobalamin Tablets in the treatment of diabetic encephalopathy and its effect on patients' serum miR-132-3p and miR-137 expression， and insulin resistance. Methods： A total of 120 patients with diabetic encephalopathy treated at the Nanyang Second General Hospital from January 2021 to October 2023 were selected and divided into a treatment group and a control group according to the random number table method， with 60 cases in each group. The control group received conventional treatment combined with Mecobalamin Tablets，while the treatment group was additionally treated with berberine based on the control group. The clinical effects and adverse reactions in the two groups were compared，as well as the blood glucose，traditional Chinese medicine syndrome scores，the expression of serum miR-132-3p and miR-137，insulin resistance indexes before and after treatment. Results：The total effective rate of clinical effects in the treatment group was 88.33%（53/60），and that in the control group was 73.33%（44/60），with the difference between the two groups being significant （P＜0.05）. After treatment， the fasting blood glucose， 2-hour postprandial blood glucose， and glycosylated hemoglobin levels in both groups were decreased compared with those before treatment （P＜0.05），and the above three levels in the treatment group were lower than those in the control group （P＜0.05）. After treatment， the traditional Chinese medicine syndrome scores of slow thinking，fatigue and somnolence，dizziness and tinnitus，and dark tongue and deep pulse in the two groups were decreased compared with those before treatment （P＜0.05），and the above four scores in the treatment group were lower than those in the control group （P＜0.05）. After treatment， the expression levels of miR-132-3p and miR-137 and the insulin resistance indexes in the two groups were decreased when compared with those before treatment （P＜0.05），and the expression levels of miR-132-3p and miR-137 and the insulin resistance indexes in the treatment group were lower than those in the control group （P＜0.05）. The incidence of adverse reactions in the treatment group was 8.33%（5/60），and that in the control group was 3.33%（2/60）；there was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. Conclusion： Berberine combined with Mecobalamin Tablets has a good therapeutic effect on diabetic encephalopathy， which can reduce the expression levels of serum miR-132-3p and miR-137 and the insulin resistance indexes in patients，with high safety.