The purpose of this project was to examine the influence of resistance exercise (RE) intensities, resulting in different total volume loads on circulating interleukin-6 (IL-6), insulin and glucose response (IGR) to a carbohydrate feeding (CHO), and whether RE-induced IL-6 was associated with postexercise IGR. Fourteen men (21.7 +/- 1.7 years, 83 +/- 14.2 kg), performed 2 RE sessions (low-intensity resulting in high volume [65% 1-repetition maximum (1RM)], LO; high intensity resulting in low volume [85% 1RM], HI); and a nonexercise control trial (CON). Resistance exercise included 3 sets (LO = 12 reps, 12 reps, and failure; HI = 8 reps, 8 reps, and failure) of 8 exercises. Blood was obtained pre- (PR) and post (PO) exercise, and 6 hours postexercise (6H). Twenty-three hours after RE or CON, participants consumed 100 g dextrose (CHO) beverage. Blood was collected before (0 minutes) and 60 minutes after CHO (n = 6, phase 1) or every 30 minutes for a 2-hour oral glucose tolerance test (n = 8; phase 2). Circulating IL-6, insulin, and glucose were analyzed via enzyme-linked immunosorbent assay, radioimmunoassay, and enzymatic methods, respectively. Total volume load was higher in LO (17,729 +/- 1,466 kg) compared with HI (13,160 +/- 1,097 kg; p < 0.001). Postexercise IL-6 was elevated (p = 0.003) in LO and HI compared with CON (7.4 +/- 1.3, 5.2 +/- 0.7, and 2.5 +/- 0.7 pg.mL, respectively), with LO IL-6 greater than HI. Areas under the curve for glucose (p = 0.081; CON: 741 +/- 46, LO: 690 +/- 28, and HI: 660 +/- 21 mM.min) and insulin (p = 0.075; CON: 6,818 +/- 1,018, LO: 5,056 +/- 869, and HI: 5,405 +/- 1,076 microIU.mL) were not different among trials (n = 8). When 0- and 60-minute values were compared (n = 14), insulin was lower at 60 minutes in LO and HI compared with CON (55 + 9.1, 83 +/- 13, 105 +/- 13 microIU.mL, respectively) with LO insulin being lower than HI (p < 0.001). No relationship was observed between PO IL-6 and IGR, but PR IL-6 was negatively related to both PR (r = -0.043, p < 0.05) and 60 minutes (r = -0.59, p < 0.01) glucose (n = 14). These results indicate that TVL contributes to RE-induced IL-6 release and that TVL may be more important than RE intensity when improvements in glucose tolerance or IS are the goal.