Abstract: Objective To study the activation of p38 mitogen-activated protein kinase (MAPK) in the brain of rabbits after craniocerebral gunshot injury in a hot and humid environment (HHE) and explore its possible mechanism. Methods Craniocerebral gunshot injury model was established in 30 New Zealand white rabbits, which were subsequently exposed to environment of normal temperature (at 22.0±0.5℃ with relative humidity of 50%) or HHE at 39.0±0.5℃ with relative humidity of 80%-85% for 10 min, 30 min, 1 h, 1.5 h, and 2 h groups, respectively, with 5 rabbits in each group. p38 MAPK activity in the brain tissues of the rabbits following the injury and environmental exposure were detected by Western blotting and analyzed semi-quantitatively by Bio-Profil gel image analysis system. Results p38 MAPK activity in the cortex and hypothalamus was significantly elevated following gunshot injury and HHE exposure, reaching the peak level at 1 h of HHE exposure and then decreased. p38 MAPK activity was significantly higher in the hypothalamus than in the cortex. Conclusion p38 MAPK activity increases in the early stage following craniocerebral gunshot injury and HHE exposure in rabbits, the mechanism of which might involve the secondary brain insult.