Abstract Background The physiological and pathophysiological mechanisms that govern diving, both self-contained underwater breathing apparatus (SCUBA) and breath-hold diving (BH-diving), are in large part well known, even if there are still many unknown aspects, in particular about cell metabolism during BH-diving. The scope of this study was to investigate changes in glycemia, insulinemia, and the catecholamine response to BH-diving, to better understand if the insulin-stimulated glucose uptake mechanism is involved in cellular metabolism in this sport. Methods Twenty male experienced healthy breath-hold divers were studied. Anthropometric information was obtained. Glycemia, insulinemia, and catecholamine response were investigated before and after the series of BH-diving. Results We found a statistically significant decrease in the blood glucose levels between before and after dives (mean 94.3 ± 11.6 vs. 83.5 ± 12.5 mg/dl) P = 0.001 and a statistically significant increase in blood insulin value (median 4.5 range 3.4/6.4 vs. 7.0 range 4.2/10.2 mcgU/ml) P < 0.0001. Also, we found a statistically significant increase of catecholamine production (median 14.0 range 8/18 vs. 15.5 range 10.0/21.0 μg) P < 0.0001. Conclusions The increase in blood insulin during BH-diving associated with the decrease of blood glucose levels could indicate that the upregulating cellular uptake is not caused by activation of the specific glucose transporters. Particular diving-related conditions such as the diving reflex, the intermittent hypoxia/hyperoxia, and the particular environmental condition could play an important role in the mechanism involved in glycemia decrease in BH-diving. Our data confirm that the adaptations to BH-diving are caused by complex mechanisms and involve many peculiar responses still in large part unknown.