Purpose The aim of this study was to identify the motivational factors and the barriers of Egyptian diabetic retinopathy (DR) patients to recruitment in clinical trials. Patients and methods This is a cross-sectional study of the patients with diabetes mellitus attending the Outpatient Clinic of Zagazig University Hospital from September 2022 to December 2022. Patients with any degree of DR were included. A questionnaire was distributed to all participants. It included the sociodemographic and clinical characteristics and questions to identify the motivational factors or the barriers to participate in a clinical trial. The patients were categorized into two groups according to their tendency for recruitment: the first group that accepted participation,who were asked about the most motivational factors and the second group that refused participation, who were asked about their potential barriers. Results The study recruited 206 DR patients of whom 145 (70.4%) accepted to participate in clinical trials, while the remaining 61 (29.6%) patients refused to participate. Fear from blindness was the commonest motivational factor (93.1%) and the risk of side effects was the commonest barrier (100%). Acceptance to participate was higher among those with positive family history of diabetes mellitus (P=0.01). Refusal to participate was higher in mild nonproliferative DR patients (P<0.001), while patients with proliferative DR and macular edema significantly accepted to participate (P<0.001). High education was significantly associated with acceptance compared to those who refused to participate (81.1 vs. 18.9%, respectively, P=0.004). Ocular history of previous intervention was significantly associated with acceptance to participate (P=0.001). Conclusion Acceptance of DR Egyptian patients to participate in clinical trials was unpredictably high. The results of this questionnaire should encourage researchers to conduct more clinical trials.