Purpose <p>This study aims to investigate the association between coagulation parameters and diabetic kidney diseases (DKD) with a specific focus on evaluating the potential mediating effects of inflammation.</p> Methods <p>A total of 10,523 patients from 6 different centers were enrolled in our study. The association between coagulation parameters and DKD was evaluated using the logistic regression model and subgroup analysis. The predictive ability of coagulation parameters for DKD was assessed through a series of investigations including receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA). Additionally, mediation analysis was performed to examine the potential role of different inflammatory factors on the association between coagulation parameters and DKD.</p> Results <p>Multivariate logistic analysis revealed that fibrinogen (FIB) (OR = 1.086, 95%CI = 1.035–1.039, p-value &lt; 0.001) and prothrombin activity (PTA) (OR = 1.015, 95%CI = 1.011–1.019, p-value &lt; 0.001) were positively associated with DKD. Conversely, prothrombin time (PT) was negatively associated with DKD when converted into a categorical variable (Tertile 3: OR = 0.701, 95%CI = 0.594–0.827, p-value &lt; 0.001). Moreover, PT, PTA, and FIB were examined for their predictive ability and PT performed best in the prediction of DKD (AUC: 0.583, 95%CI: 0.569–0.598). Mediation analysis demonstrated that neutrophils attenuated 8.27% of the total effects in the DKD-PTA relationship and mediated 3.74% of the relationship between DKD and PT. Moreover, multiple inflammation parameters including eosinophils and albumin were also found to mediate the association between DKD and coagulation parameters.</p> Conclusion <p>These findings suggest that coagulation parameters are cost-effective screening tools for early DKD detection. Inflammation parameters are identified to mediate the association between coagulation parameters and DKD while the internal mechanism requires further exploration.</p>