OBJECTIVE The objective of this study was to establish diagnostic technology to automatically grade the severity of diabetic retinopathy (DR) according to the ischemic index and leakage index with ultra-widefield fluorescein angiography (UWFA) and the Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field (7-SF). METHODS This is a cross-sectional study. UWFA samples from 280 diabetic patients and 119 normal patients were used to train and test an artificial intelligence model to differentiate PDR and NPDR based on the ischemic index and leakage index with UWFA. A panel of retinal specialists determined the ground truth for our data set before experimentation. A confusion matrix as a metric was used to measure the precision of our algorithm, and a simple linear regression function was implemented to explore the discrimination of indexes on the DR grades. In addition, the model was tested with simulated 7-SF. RESULTS The model classification of DR in the original UWFA images achieved 88.50% accuracy and 73.68% accuracy in the simulated 7-SF images. A simple linear regression function demonstrated that there is a significant relationship between the ischemic index and leakage index and the severity of DR. These two thresholds were set to classify the grade of DR, which achieved 76.8% accuracy. CONCLUSIONS The optimization of the cycle generative adversarial network (CycleGAN) and convolutional neural network (CNN) model classifier achieved DR grading based on the ischemic index and leakage index with UWFA and simulated 7-SF and provided accurate inference results. The classification accuracy with UWFA is slightly higher than that of simulated 7-SF.