To quantitatively evaluate the effect of insulin on cardiac sympathetic nerve activity (SNA) and analyze clinical factors associated with insulin sensitivity for the regulation of SNA in diabetics, 29 Japanese type 2 diabetics without neuropathy were recruited. A 2-h control study and a 2-h hyperinsulinemic euglycemic glucose clamp study were performed. From the power spectral analysis of R-R intervals on ECG during both studies, two major components, the low-frequency (LF) and the high-frequency component (HF), were obtained. Then %LF was calculated as LF/(LF +HF), and the ratio of the average %LF during the last 30 min of the clamp or the control to the average %LF for the entire time for clamp or control (R-%LF) was used as a marker of changes in SNA. R-%LF was significantly higher during the clamp than in the control (1.07 ± 0.04 vs. 1.03 ± 0.03, P < 0.05). High responders (individual R-%LF during clamp  mean + 2SD in control) showed a higher basal mean blood pressure (BP) before the clamp (89 ± 3 vs. 82 ± 2, P < 0.03) but not a higher glucose infusion rate (GIR) compared with low responders (<mean + 2SD). Furthermore, R-%LF showed a positive correlation with basal mean BP (P < 0.02) but not with GIR. These data demonstrate that an acute insulin load stimulates cardiac SNA, and insulin sensitivity in the regulation of SNA may be associated with BP regulation independently of peripheral insulin sensitivity.