Objective:To investigate the effect of Shenfu injection(SFI) on the expression of Interleukin-18(IL-18) and Interleukin-1β(IL-1β) in neonatal rats with hypoxic - ischemic brain damage(HIBD), and clarify the protection of SFI for HI brain damage at the molecular level. Methods:Seven-day-old Sprague-Dawley rats were randomly assigned to sham operation group(S), normal sodium control group(C) and Shenfu injection treatment group(SF), and Models of postnatal 7-day Sprague Dawley(SD) rats with HIBD were established by the Rice method. They were further divided into five subgroups(n = 8 per subgroup) according to the time points 3 h,12 h,24 h,6d and 14 d. In each subgroup, rats were used to examine the level of IL-18,IL-1β in brain homogenates by ELISA. Results:The level of IL-1β was significantly higher in group C and group SF higher than that in group S at the time point 12 h, 24 h, 6 d(P < 0.01); The levels of IL-18 in group C and group SF were significantly higher than that of group S at the time point 24 h, 6 d, 14 d(P < 0.01); The expression of IL-1β in group C peaked at 12 h after HI insult and decreased after this, There was no difference in group S and group C at 14 d(P > 0.05); The expression of IL-18 in group C began to increase at 24 h after HI insult(P < 0.01), peaked at 6 d after HI insult and decreased after this. But IL-18 was still higher than group S(P < 0.01) at 14 d;the level of IL-1β in brain homogenates after HI insult in group SF were lower than group C at 12 h,24 h,6 d(P < 0.01); the level of IL-18 in brain homogenates after HI insult in group SF were lower than group C at every observed spot after 12 h(P < 0.01). Conclusion:The level of IL-18 and IL-1β in cerebral cortex had increased after HI insult in neonatal rats and SFI can decrease the level of IL-18 and IL-1β in cerebral cortex. SFI has a protedive function in neonatal rats after HI insult.