Background: Diabetes Mellitus is an endocrine disorder, characterized by hyperglycemia that is, highblood sugar levels. Insulin is one of the oldest valuable anti-diabetic medications available and also the most effective agent in dropping hyperglycemia when used in appropriate doses. Simulation-based education serves as a link between classroom learning and clinical practice. This study aimed to investigate the effect of simulation-based education on nurses' performance regarding insulin self-injection for diabetic patients. Method: A quasi-experimental design was used to conduct this study (pre/post-test one group). Setting: The study was conducted in the Diabetic Inpatient and Outpatient Clinic at Specialized Medical Hospital, Mansoura University. Subjects: The study subjects were included a convenient sample of all available staff nurses (50) working in previous selected setting. Tools for data collection: Tool (I) Insulin self-injection questionnaire and Tool (II): Insulin self-injection observational checklist (pre/posttest). Results: Between the knowledge and practice of the nurses under study, there was a very statistically significant difference (P<0.001). Before implementing the simulation-based education, the study found that (66%) of the nurses had poor knowledge and 74% had unsatisfactory practice with insulin self-injection for patients with diabetes. Following the implementation of simulation-based education, (94%) of the nurses in the study demonstrated a satisfactory level of practice and a good level of knowledge (92%). After the simulation-based intervention, nurses' performance improved and changed in a highly statistically significant way compared to before (P<0.001). Conclusion: According to the current study's findings, simulation-based education has a positive effect on improving nurses' performance regarding insulin self-injection for diabetic patients post simulation-based education. Recommendations: According to the study, the gaps in knowledge about self-administration of insulin injections should be addressed with appropriate instruction and an insulin injection demonstration. Comprehensive insulin usage education programs that emphasize empowering insulin use among patients with diabetes mellitus and related information should be widely accessible as essential elements of diabetes mellitus management programs.