Background GDF15 is emerging as valuable biomarker in cardiovascular disease and diabetic kidney disease. Also, GDF15 represents an early response gene induced after tissue injury and studies performed in GDF15 knockout mice suggest that GDF15 plays a protective role after injury. In the current study, we investigated the role of GDF15 in the development of diabetic kidney damage in type 1 and type 2 models of diabetes. Methods and results Renal damage was assessed in GDF15 knockout (ko) mice and wild type (wt) mice in streptozotocin type 1 and db/db type 2 diabetic models. Genetic deletion of GDF15 augmented tubular and interstitial damage in both models of diabetes, despite similar diabetic states in ko and wt mice. Increased tubular damage in ko animals was associated with increased glucosuria and polyuria in both type 1 and type 2 models of diabetes. In both models of diabetes, ko mice showed increased interstitial damage as indicated by increased α-SMA staining and collagen type 1 expression. In contrast, glomerular damage was similarly elevated in diabetic ko and wt mice. In type 1 diabetes, GDF15 ko mice demonstrated increased expression of inflammatory markers. In type 2 diabetes, elevated levels of plasma creatinine indicated impaired kidney function in ko mice. Conclusion GDF15 protects the renal interstitium and tubular compartment in experimental type 1 and 2 diabetes without affecting glomerular damage.