Background: Leprosy, is a chronic infectious illness caused by Mycobacterium leprae which, also known as Hansen's disease, which consider a major health problem globally and in Egypt. Aim: The study aimed to enhance self-care program for patients with leprosy grade 2 in Abu Zaabal Leprosy Colony. Study design: To perform this study a quasiexperimental design was used. Subject: A purposive sample composed of 85 patients with age ranged from 25: 60 years and diagnosed as G2Ds. Setting: This study was conducted at Abu Zaabal Leprosy Colony. Tools: It was composed of two-tools. First tool: An interviewing questionnaire to assess socio-demographic characteristics of patients, their knowledge, practices, and health problems. Second tool: An observational checklist: to assess patients' independence level of daily living activities. Results: The findings of this study revealed that 76.5% of the study participants had unsatisfactory knowledge about leprosy before program implementation and improved to 92.9% post program and 84.7% at follow up as well the practices were inadequate before program and enhanced for 94.1% post program and 89.4% at follow up with significant statistical relations between patients' knowledge/practices and their independence level, social, and psychological health problems as well as their age, gender, and educational level, through program implementation phases (P< .0001). Conclusion: The self-care program had improved patients' knowledge and practices related to leprosy, which affected in a positive impact on restoring their health and improving their independence level. Recommendation: The study recommended that, publication, and dissemination of self-care program in all leprosy colony and any health care services to raise awareness about leprosy and its prevention.