Physical exercise increases the level of endogenous opiates that possibly play a major role for integration of hormonal and metabolic responses to exercise. Increased endogenous opioids in response to physical activity may enhance the performance through decreasing pain perception. However, what possible effect the opioid peptides have on physical exercise at the level of central nervous system remains to be elucidated. In this study, naloxone (N = 6), and naltrindole (N = 8) were administered intracerebroventrically to rats. A physiologic saline group (N = 10) and a control group (N = 8) were also included in the study. All groups were then subjected to exhaustive exercise on a treadmill. Besides recording the exhaustion time, blood glucose and lactate levels were measured before and after exercise. Treatments with naloxone and naltrindole had no effect on the exhaustion time. In comparison with pre-exercise period, lactate levels increased, while glucose levels decreased significantly in the blood of all animals during post-exercise period. However, decreased level of glucose in the post-exercise period was statistically significant only in those treated with naltrindole, compared with the other groups. Our findings indicate that the central endogenous opioid peptides may have a role in the regulation of glucose metabolism during exhaustive exercise. This effect can be mediated via delta opioid receptors, although they exert no effect on the performance, namely, on the exhaustion time.