Background <p>Diabetic patients often experience prolonged hyperglycemia, which leads to sustained harm and malfunction of various body organs. The blood urea nitrogen (BUN) to serum albumin ratio (BAR) and systemic inflammation response index (SIRI) have been proven to be reliable indicators. We aimed to investigate the association of BAR, SIRI and their combination with the risk of diabetic macrovascular diseases.</p> Methods <p>A total of 2,911 participants from Nanfang Hospital diagnosed with type 2 diabetes mellitus (T2DM) were included. Restricted cubic spline (RCS) and logistic regression modelling were used to assess the relation between different values of BAR, SIRI and combined BAR-SIRI and the risk of diabetic macrovascular complications. Receiver operating curve (ROC) analysis was used to compare the predictive value of BAR, SIRI, and their combination for macrovascular outcomes.</p> Results <p>High value of BAR, SIRI and their combination were associated with increased risk of macrovascular complications (BAR: odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.18–1.78; SIRI: OR(95% CI) = 1.25(1.03,1.52); BAR-SIRI: OR(95%CI) = 1.51(1.21,1.88); all <i>p</i> &lt; 0.05). ROC curve analysis demonstrated that combined BAR-SIRI has the best predictive value for risk of macrovascular outcomes (area under the ROC curve [AUC]: BAR-SIRI: 0.678 &gt; SIRI: 0.674 &gt; BAR: 0.673).</p> Conclusion <p>BAR, SIRI and their combination exhibit a notable positive correlation with the risk of diabetic macrovascular disease and may be independent predictors of macrovascular complications.</p> Clinical trial registration <p>ClinicalTrials.gov, TRN: NCT06651983, Registration date: 19 May 2025.</p> Graphical abstract <p></p>