Increasing evidence suggests that renal inflammation contributes to the pathogenesis and progression of diabetic kidney disease (DKD) and that anti-inflammatory therapies might have renoprotective effects in DKD. Immune cells and resident renal cells that activate innate immunity have critical roles in triggering and sustaining inflammation in this setting. Evidence from clinical and experimental studies suggests that several innate immune pathways have potential roles in the pathogenesis and progression of DKD. Toll-like receptors detect endogenous danger-associated molecular patterns generated during diabetes and induce a sterile tubulointerstitial inflammatory response via the NF-κB signalling pathway. The NLRP3 inflammasome links sensing of metabolic stress in the diabetic kidney to activation of pro-inflammatory cascades via the induction of IL-1β and IL-18. The kallikrein–kinin system promotes inflammatory processes via the generation of bradykinins and the activation of bradykinin receptors, and activation of protease-activated receptors on kidney cells by coagulation enzymes contributes to renal inflammation and fibrosis in DKD. In addition, hyperglycaemia leads to protein glycation and activation of the complement cascade via recognition of glycated proteins by mannan-binding lectin and/or dysfunction of glycated complement regulatory proteins. Data from preclinical studies suggest that targeting these innate immune pathways could lead to novel therapies for DKD.