Objective:To investigate the protective effect of chrysin on the newborn rats with ischemic hypoxic brain damage and its related mechanism.Methods:The rats were randomly divided into sham-operated group, model group, low and high-dosage group of chrysin with 12 rats in each group. Except sham-operated group, the rats in other three groups were used as hypoxic-ischemic encephalopathy model. After the modeling, the rats in the low and high dosage groups were intraperitoneally injected with 30 mg/kg and 60 mg/kg chrysinimmediately, while the rats in the sham-operated group and the model group were intraperitoneally injected with equal volume of normal saline for 4 days. The HE staining was used to observe the protective effect of drugs on brain. The superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) levels in cells were measured by biochemical method. Western blot was used to detect the expression of heme oxygenase-1 (HO-1) and transcription factor NF-E2-related factor 2 (Nrf2).Results:The neurons in the cortex of rats in sham-operated group were arranged orderly with round nuclei and obvious nucleoli; the brain tissue of rats in model group showed edema and the arrangement of neurons was loose, the degeneration and necrosis of neurons in low and high dosage of chrysin groups were less than those in model group. Compared to the model group, the SOD activity (55.74 ± 5.14 U/mg, 69.84 ± 5.05 U/mg vs. 37.64 ± 6.41 U/mg) and CAT activity (2.44 ± 0.22 U/mg, 2.59 ± 0.42 U/mg vs. 2.08 ± 0.37 U/mg) in the brain tissue of rats in the low and high dose group were significantly increased ( P<0.05). The MDA level (3.74 ± 0.05 mmol/mg, 2.60 ± 0.18 mmol/mg vs. 4.35 ± 0.24 mmol/mg) in rat brain tissue of low and high dose group was significantly decreased ( P<0.05). The expressions of HO-1 (0.43 ± 0.08, 1.02 ± 0.15 vs. 0.14 ± 0.07) and Nrf2 (0.48 ± 0.07, 0.79 ± 0.09 vs. 0.26 ± 0.08) protein in rat brain tissue of low and high dose group were significantly decreased ( P<0.05). Conclusions:The chrysin could alleviate nerve injury in rats with hypoxic-ischemic encephalopathy, and its mechanism may be related to the up-regulated HO-1 and Nrf2 protein expression.