Serum fatty acid-binding protein 4 (FABP4) has been linked to renal dysfunction. This study evaluated the association between serum FABP4 and the radioisotope glomerular filtration rate (rGFR) in type 2 diabetic patients (T2DM) with early diabetic nephropathy. Twenty healthy controls and 172 patients with T2DM were enrolled. Serum FABP4 and renal impairment biomarkers including urinary albumin-to-creatinine ratio (UACR), serum retinal-binding protein 4 (RBP4), urinary cystatin C-to-creatinine ratio (CysC/Cr), and neutrophil gelatinase-associated lipocalin-to-creatinine ratio (NGAL/Cr) were measured. Diethylenetriaminepentaacetic acid (99mTc-DTPA) was used to test rGFR. Serum FABP4 levels were higher in T2DM patients compared with the controls. There was no significant correlation between serum FABP4 and UACR in patients with T2DM. Multivariate stepwise regression analysis showed that, in patients with T2DM, FABP4 was significantly associated with rGFR while CysC/Cr and RBP4 were significantly associated with UACR independently. But UACR had no independent association with rGFR. NGAL/Cr had no significant correlation with either rGFR or UACR. FABP4 might be an early biomarker for diabetic nephropathy if combined with UACR.