Objective To explore the interaction between health literacy, emotional distress and self-management in type 2 diabetes mellitus. Methods A total of 239 patients with type 2 diabetes were selected by convenience sampling, who were admitted to the Department of Endocrinology and Metabolism of 2 level-A tertiary hospitals in Zhenjiang from September 2019 to April 2020. An investigation was made of the relationship between health literacy in type 2 diabetes, emotional distress and self-management. Using AMOS 24.0, Pearson correlation analysis established a structural equation model to verify the mediating effect. Results The score of health literacy was 61.91. Pearson correlation analysis showed that emotional distress was negatively correlated to self-management (r=-0.352, P<0.001) and health literacy (r=-0.479, P<0.001), and that health literacy and self-management had positive correlation (r=0.345, P<0.001). In the mediation test, health literacy was a mediating variable between emotional distress and self-management, with a mediating effect value of 41.67%. Conclusion Health literacy partially mediates emotional distress and self-management in the patients with type 2 diabetes mellitus. Clinicians should pay attention to improving the health literacy of patients with emotional distress to improve the patients′ self-management.