ObjectivesThis study aimed to identify risk factors for diabetic retinopathy (DR) and develop machine learning (ML)-based predictive models using routine laboratory data in patients with type 2 diabetes mellitus (T2DM).MethodsClinical data from 4259 T2DM inpatients at Beijing Tongren Hospital were analyzed, divided into a model construction data set (N = 3936) and an external validation data set (N = 323). Using 39 optimal variables, a prediction model was constructed using the eXtreme Gradient Boosting (XGBoost) algorithm and compared with four other algorithms: support vector machine (SVM), gradient boosting decision tree (GBDT), neural network (NN), and logistic regression (LR). The Shapley Additive exPlanation (SHAP) method was employed to interpret the XGBoost model. External validation was performed to assess model performance.ResultsDR was present in 47.69% (N = 1877) of T2DM patients in the model construction data set. Among the models tested, the XGBoost model performed best with an AUC of 0.831, accuracy of 0.757, sensitivity of 0.754, specificity of 0.759, and F1-score of 0.752. SHAP explained feature importance for XGBoost model and identified key risk factors for DR. External validation yielded an accuracy of 0.650 for the XGBoost model.ConclusionsThe XGBoost-based prediction model effectively assesses DR risk in T2DM patients using routine laboratory data, aiding clinicians in identifying high-risk individuals and guiding personalized management strategies, especially in medically underserved areas.