Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C represent early renal injury markers for contrast-induced nephropathy (CIN). Baseline parameters such as type and quantity of contrast, patient preparation, renal function status, and diabetes mellitus (DM) are known to affect the response of the kidney to contrast-induced injury. This study was taken up to know the biomarker response to contrast administration in 58 diabetic and 59 nondiabetic male patients with same baseline parameters and baseline serum creatinine <1.2 mg/dl undergoing coronary angiography and their role in predicting the development of CIN. Serum creatinine, serum cystatin C, and urinary-NGAL (u-NGAL) were analyzed at baseline (0 h), 4 h, and 24 h after the administration of contrast medium. CIN was defined as a 25% increase in serum creatinine concentration from the baseline value or an absolute increase of at least 0.5 mg/dl within 48 h after the administration of contrast media. Serum creatinine rose 24 h after contrast administration in the diabetic group compared to 48 h in the nondiabetic group. Serum cystatin C levels rose 24 h after contrast administration in both the groups. The earliest marker to rise in both the groups was u-NGAL at 4 h. Diabetic patients had significantly higher u-NGAL (P = 0.005), and serum creatinine levels (P = 0.008) 4 h, and 24 h after contrast administration, respectively. Serum creatinine and u-NGAL/creatinine at 4 h were found to be the best predictors of CIN in the DM and non-DM patients, respectively. Biomarker response to contrast administration is different in diabetic and nondiabetic patients following contrast administration. Diabetic patients exhibit early and greater degree of renal impairment compared to the nondiabetic patients irrespective of the outcome. We propose the use of serum creatinine in patients with DM and u-NGAL/creatinine in non-DM patients to identify CIN as early as 4 h after contrast administration.