Objective：To observe the change of microglia activity after fast decompressing and/or hyperbaric oxygenation （HBO）-induced central nervous system （CNS） damage, so as to study the role of microglia in CNS dysbaric injury and the effects of HBO on microglia. Methods.. Rats were randomly divided into the following groups., normal control, safe decompressing, fast decompressing （FD） injured, and HBO treated groups. Rat models of dysbaric injury were established by FD; 6 h later the rat models were subjected to HBO treatment. The activated microglia were detected by FITC-linked Isolectin B4; TNF-α and TNF-α converting enzyme （TACE） positive cells were detected immunohistochemically; and neural apoptosis was detected by TUNEL assay. TNF-α contents in CNS tissue were determined by ELISA and the bioactivity of sTNF-α in cerebrospinal fluid （CSF） were determined by L929 cell cytotoxicity bioassay. Results： IB4 positive microglia appeared in rats＇ CNS 6 h after FD treatment, peaked after 24 h, and declined thereafter. The activated microglia had morphological changes. Cell apoptosis indices of CNS reached its peak 48 h after FD treatment. Activated microglia and apoptotic neurons had similar distribution. TNF-α was detected in the brain and spinal cord 6 h after FD, significantly increased after 24 h, and peaked after 48 h. The content of TNF-α was positively correlated with IB4 positive cells and apoptosis index （P〈0.05）. TNF-α bioactivity in CSF of FD group had a similar change to TNF-α content in CNS tissue. The IHC results showed that, TNF-α and TACE positive cells had the same morphology and distribution to those of IB4 positive cells. HBO treatment significantly decreased IB4 positive cells after 24 h, 48 h, and 72 h, reduced TNF-α content in CNS tissues and TNF-α cytotoxicity in CSF; and decreased the apoptosis index after 48 h and 72 h. Conchlusion： Microglial cells are quickly activated after dysbaric-induced injury of CNS. The activated microglia play a role in secondary injury through increasing TNF-α and TACE expression. HBO therapy can protect the neurons through depressing the activation and proliferation of microglia and reducing secretion of neurotoxin.