Background: Type 2 diabetes mellitus is considered a serious, an increasing global health burden, and leading cause of premature morbidity and worldwide mortality due to its complications. Aim: This study aimed to examining the effect of instructional program on knowledge regarding adherence to therapeutic regimen among type 2 diabetic patients. Subjects and method: Design: A quasi-experimental research design was utilized.  Setting: This study was carried out at diabetic out-patient clinic in Medical Specialized Hospital affiliated to Mansoura University. Subjects: a sample of 53 participants who fulfilled the inclusion criteria of the study was selected. Tool:  A structured interview which included four parts was used in carrying out this study. Results; 73.6% of the studied patients were females; and 79.2% had low socioeconomic level. Regarding the total score level of knowledge, 84.9% of the studied sample had satisfactory score level after applying the instructional program, 98.1% of them had satisfactory beliefs after applying the instructional program. And, 58.5% of the sample had high score level of adherence after applying the instructional program. The mean ±SD of glycosylated hemoglobin of the subjects was decreased significantly from 9.5±1.7 to 7.9±1.2 after applying the instructional program. Conclusion and Recommendations; improving diabetic patients' knowledge regarding type 2 diabetes mellitus was very important for improving adherence to the therapeutic regimen .Developing instructional plan based on issues related to diabetic regimen and personal perceptions that militate against adherence.