Abstract: Objective To examine the changes in expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein, p-PTEN protein and Bim (Bcl-2 interacting mediator of cell death) mRNA in the cortex of neonate rat brains with hypoxic-ischemic brain damage (HIBD) and to explore the mechanisms of neuroprotective effects of PTEN inhibition. Methods One hundred and twenty-eight neonate (10 days) SD rats were divided into four groups: hypoxia-ischemia (HI), sham control (Sham), bisperoxovanadium (bpv), and normal saline (NS) group. Rats in the HI group had their right common carotid arteries (CCA) exposed and ligated, and were then exposed to hypoxia in a chamber filled with 8% oxygen (balanced with nitrogen) for 2.5 h. Rats in the sham control group had their right CCA surgically exposed without ligation and exposure to hypoxia. Rats in the bpv treated group received intraperitoneal injections of bpv, 30 min before HI was induced. Instead of bpv, rats in the NS-treated group received intraperitoneal injections of NS. Cerebral cortex samples of the rats were collected 0.5 h and 24 h after hypoxia. Western blot was used to detect the protein expression of PTEN, p-PTEN and Bim. Real-Time PCR was used to detect the level of Bim mRNA. TUNEL staining was used to detect apoptotic cells. Results No significant changes of PTEN protein were observed in the rats exposed to HI. However, p-PTEN protein decreased in the rats exposed to HI (0.5 h and 24 h) compared with those exposed to sham surgery (P<0.01). Compared with the sham controls, Bim mRNA and protein increased in the rats exposed to HI (0.5 h, P<0.01) and then returned to the baseline level 24 h after HI. No significant changes of PTEN protein were observed in the bpv-treated rats. However, p-PTEN protein increased and Bim mRNA and protein decreased in the bpv-treated rats (0.5 h and 24 h, P<0.01) compared with those in the HI group and NS-treated group. TUNEL positive cells also reduced in the bpv-treated rats (24 h, P<0.01) compared with those in the HI group and NS-treated group. Conclusion PTEN activities increase in the brains of neonate rats with hypoxic-ischemic brain damage. PTEN activity inhibition can decrease the level of pro-apoptotic protein Bim mRNA, leading to reduction of neuronal apoptosis.