Introduction: Previous studies highlighted that bubble-induced platelet aggregation is a predictor index of decompression sickness (DCS) severity in animal and bubble formation after a single air dive in man. The present study purpose to investigate plasmatic indexes of coagulation system and platelet activation in our rat model of DCS. Methods: Male Sprague-Dawley rats were assigned to one experimental group with an hyperbaric exposure and one control group maintained at atmospheric pressure. Rats were compressed to 1000 kPa (90 msw) for 45 min while breathing air. Onset of death time and DCS symptoms were recorded during a 30 min observed period after surfacing. Plasmatic indexes were platelet factor 4 (PF4) for platelet activation, soluble glycoprotein V (sGPV) for thrombin generation and thrombin-antithrombin complexes (TAT) for coagulation system. Blood samples for platelet count (PC) and markers were taken 3 weeks before the experimental protocol and within the 30 min after surfacing. Results: We confirmed a correlation between the percentage fall in PC and DCS severity. Plasmatic levels of sGPV and PF4 were significantly increased after the hyperbaric exposure, with no change in the control group. Discussion: The present study confirms platelet consumption as a potential index for evaluating decompression stress and DCS severity. The results point to the participation of thrombin generation in the coagulation cascades and platelet activation in bubble-induced platelet aggregation. In our animal model of DCS, the results cannot prejudge the mechanisms of platelet activation between bubble-induced vessel wall injury and bubble-blood components interaction.