Diving acclimatization refers to a reduced susceptibility to acute decompression sickness (DCS) in individuals undergoing repeated compression-decompression cycles. We postulated that mechanisms responsible for the acclimatization are similar to that of a stress preconditioning. In this study, we investigated the protective effect of prior heat shock treatment on air embolism-induced lung injury and on the incidence of DCS in rats. We exposed rats (n=31) to a pressure cycle that induced signs of severe DCS in 48% of the rats, greater wet-to-dry ratio (W/D) of lung weight, and higher protein concentration in bronchoalveolar lavage (BAL) fluid compared with those in the control group (5.48±0.69 vs. 4.70±0.17 and 362±184 vs. 209±78 mg/L, respectively). Rats with DCS expressed more heat shock protein 70 (HSP70) in the lungs than those without signs of disease. Prior heat shock (n=12) increased the expression of HSP70 in the lung and attenuated the elevation of W/D of lung weight (5.03±0.17) after the identical decompression protocol. Prior heat shock reduced the incidence of severe DCS by 23% but failed to reach statistically significant (X²=1.94, p=0.163). Venous air infusion (1.0 ml/40 min) caused profound hypoxemia (54.5±3.8 vs. 83.8±3.2 mmHg at baseline, n=6), greater W/D of lung weight (5.98±0.45), and high protein concentration in BAL fluid (595±129 mg/L). Prior heat shock (n=6) did not alter the level of hypoxemia caused by air embolism, but accelerated the recovery to normoxemia after stopping air infusion. Prior heat shock also attenuated the elevation of W/D of lung weight (5.19±0.40) and the increase in BAL protein (371±69 mg/L) in air embolism group. Our results showed that the occurrence of DCS after rapid decompression is associated with increased expression of a stress protein (HSP70) and that prior heat shock exposure attenuates the air bubble-induced lung injury. These results suggest that bubble formation in tissues activates a stress response and stress preconditioning attenuates lung injury on subsequent stress, which may be the mechanism responsible for diving acclimatization.