The aim of this study was to assess the effects of metabolic and autonomic nervous control on high-intensity resistance training (HRT) as determined by pancreatic glucose sensitivity (GS), insulin sensitivity (IS), blood lactate ([La]), and heart rate variability (HRV) in rats. Thirty male, albino Wistar rats (292 +/- 20 g) were divided into 3 groups: sedentary control (SC), low-resistance training (LRT), and HRT. The animals in the HRT group were submitted to a high-resistance protocol with a progressively increasing load relative to body weight until exhaustion, whereas the LRT group performed the same exercise regimen with no load progression. The program was conducted 3 times per week for 8 weeks. The [La], parameters related to the functionality of pancreatic tissue, and HRV were measured. There was a significant increase in peak [La] only in the HRT group, but there was a reduction in [La] when corrected to the maximal load in both trained groups (LRT and HRT, p < 0.05). Both trained groups exhibited an increase in IS; however, compared with SC and LRT, HRT demonstrated a significantly higher GS posttraining (p < 0.05). With respect to HRV, the low-frequency (LF) band, in milliseconds squared, reduced in both trained groups, but the high-frequency band, in milliseconds squared and nu, increased, and the LF in nu, decreased only in the HRT group (p < 0.05). The HRT protocol produced significant and beneficial metabolic and cardiac autonomic adaptations. These results provide evidence for the positive benefits of HRT in counteracting metabolic and cardiovascular dysfunction.