Background <p>A large body of evidence supports the long-term benefits of intensive glycemic control for patients with type 2 diabetes mellitus (T2DM). However, the relationship between intensive glycemic control and diabetic retinopathy (DR) progression in T2DM patients in the short-term remains under debate. Therefore, we investigated the effect of intensive glycemic control on DR changes in the short-term.</p> Methods <p>A total of 254 patients with T2DM, all exhibition hemoglobin A_1c (HbA_1c) levels above 7% were included in the study. We collected HbA_1c values at baseline and after 12-months. HbA_1c control classified into two categories: intensive control, targeting an HbA_1c of less than 7%, and less intensive control, targeting an HbA_1c of 7% or higher at 12-month follow-up. The severity of DR were graded based on seven-field 45° conventional fundus photographs examinations according to the United Kingdom National Diabetic Eye Screening Program guidelines.</p> Results <p>After a one-year follow-up, 129 participants achieved a target HbA_1c of less than 7% and 125 achieved 7% or more. We found no significant difference in DR changes (incidence, progression, or regression) between two groups after adjustments for age and gender. Further adjustments for confounding factors such as body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), diabetes duration, insulin use and baseline HbA_1c, revealed no association between intensive glycemic control and the DR changes.</p> Conclusions <p>This prospective cohort study demonstrates that intensive glycemic control did not associated with DR changes in T2DM patients in the short term. Further research is required to ascertain the long-term effects of intensive glycemic control on DR.</p> Trial registration <p>The trail has been registered at The UK’s Clinical Study Registry (<a href="https://www.isrctn.com">https://www.isrctn.com</a>) on 2020/04/13 (ISRCTN15853192).</p>