To investigate the potential mechanism and protective effect against brain tissue damage in rats by selenium-rich treatment after acute carbon monoxide(CO) poisoning. Methods: A total of 60 SD rats were randomly assigned to groups blank control(BC), CO poisoning(CO), low dose selenium treatment(L-Se), medium dose selenium treatment group (M-Se), and high dose selenium treatment group (H-Se), with 12 rats per group. Rats were intraperitoneally injected with CO to establish animal models of acute CO poisoning while those in the control group were injected with an equal volume of air. 30 days before and every day after generating model, rats were treated with H2O or various doses of selenium-rich drug. 7 and 14 days after generating model, cerebral cortical tissue and peripheral tissues were collected, HE staining was performed on peripheral tissue organs to observe structural changes. Immunohistochemistry and Western blot were performed on cortical tissue to assess levels of parvalbumin (PV) and Caspase-3 protein expression. Results: CO poisoned rat peripheral tissues sustained no significant injury from selenium treatment. The average PV positive cells in the 7-day and 14-day poisoning groups were significantly reduced compared to the H-Se group (P<0.05); reduction in the 7-day and 14-day poisoning groups was slightly significant compared to those in the L-Se group and M-Se group (P> 0.05). There was no significant difference in PV positive cells between the BC group and H-Se group. PV level in the 7-day and 14-day H-Se treatment groups was significantly higher than that in the CO group(P<0.05) and Caspase-3 level was lower than the CO group (P<0.05). There was no significant difference in PV and Caspase-3 level between the 7-day and 14-day H-Se treatment groups and the BC group (P>0.05). There was no significant difference in PV and Caspase-3 level between groups L-Se, M-se and CO group at 7-day and 14-day (P>0.05). Conclusion: High doses of selenium treatment can markedly increase the level of PV and reduce the activation of Caspase-3