To characterize early blood and tissue markers predictive of decompression sickness (DCS), this study focused on identifying changes in inflammatory mediators during the 24-h period immediately following compression-decompression of female Sprague-Dawley rats. Early blood and tissue markers predictive of DCS include inflammatory cytokines and cell adhesion molecules (CAMs). Increased levels of inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon-gamma (IFN-gamma), were detected in the circulation 6 h after decompression. Increased levels of only IL-6 were observed at 24 h. Compared with control animals maintained at 1 atmospheres absolute pressure ATA (101 kPascal), significant increases in expression of E-selectin, and L-selectin, as well as intercellular adhesion molecule-1 (ICAM-1), were observed immunohistochemically in the lungs and brains of the rats 6 h after exposure to 2 (203 kPascal), 3 (303 kPascal), or 4 (404 kPascal) ATA, followed by rapid decompression. These levels drop by 24 h. In contrast to the observations in brain, greater increases in expression of E-selectin and L-selectin around vessels and connective tissue were seen at 24 h after decompression in the quadriceps of rats exposed to either 3 or 4 ATA. Significant increases in expression of the A(2A) receptor, which modulates inflammation by downregulating production of these cytokines, were detected only in the quadriceps removed at 24 h after decompression from 4 ATA. This study demonstrated that rapid decompression induces the release of mediators of inflammation and resulting tissue inflammation cascades, as well as a protective anti-inflammatory response.