The chemokine receptor CCR2 is central for migration of monocytes into inflamed tissues. The novel CCR2 antagonist CCX140-B, which is currently in two separate Phase 2 clinical trials in diabetic nephropathy, was recently shown to reduce hemoglobin A1c and fasting blood glucose levels in Type 2 diabetics. In this report, we describe the effects of this compound on glycemic and renal function parameters in diabetic mice. Since CCX140-B has low affinity for mouse CCR2, transgenic human CCR2 knock-in mice were generated and rendered diabetic either with a high-fat diet (DIO) or by deletion of the leptin receptor gene (db/db). CCX140-B treatment in both models resulted in decreased albuminuria, which was associated with decreased glomerular hypertrophy and increased podocyte density. Moreover, treatment of DIO mice with CCX140-B resulted in decreased levels of fasting blood glucose and insulin, normalization of HOMA-IR values, and decreased numbers of adipose tissue inflammatory macrophages. Unlike other CCR2 antagonists, CCX140-B had no effect on plasma levels of the CCR2 ligand CCL2 or on the numbers of blood monocytes. These results support the ongoing evaluation of this molecule in diabetic subjects with impaired renal function.