OBJECTIVE: Intrauterine growth retardation (IUGR) may contribute to the disorder of brain development of fetuses. Because ligustrazine has been proved to be effective in improving blood circulation and relieving clot formation, it has been used to treat hypoxic-ischemic brain damage of the newborn. This study aimed to explore the effect of ligustrazine on the brain development in fetal rats with IUGR induced by passive smoking and its mechanism. METHODS: Thirty-six pregnant rats were randomly assigned into four groups: Control, Model, Low dose (40-mg/kg ligustrazine) and High dose (80-mg/kg ligustrazine) (n=9 each). IUGR was induced by passive smoking in rats from the last three groups. Ligustrazine was administered for the last two groups between day 8 and day 20 of gestation. On day 21 of gestation, the fetal rats were delivered by cesarean section. The body weight, brain weight, liver weight, body length and tail length of fetal rats were measured. The levels of nitric oxide(NO), malondialdehyde(MDA) and superoxide dismutase(SOD) activity in the brains of fetal rats were examined. RESULTS: The incidence of IUGR in the Control, Model, and the Low and High dose ligustrazine treated groups was 3.9%(4/105), 55.0%(50/106), 11.8%(11/103) and 5.4%(5/99) respectively. The average body weight(3.1±0.3-g vs 3.8±0.6-g), brain weight (0.144±0.012-g vs 0.176±0.018-g)and liver weight (0.29±0.06-g vs 0.34±0.07-g)of fetal rats in the Model group were all significantly lower than those of the Control group(P<0.01). Those in the two treatment groups were significantly higher than in the IUGR group. The levels of NO (52.4±1.4-μmol/g vs 43.7±6.7-μmol/g)and MDA (273.5±8.5-μmol/g vs 249.6±6.2-μmol/g)in the brains of fetal rats of the Model group increased significantly compared with those of the Control group(both P<0.01), but the activity of SOD of the Model group decreased compared with the Control group(29.7±2.6-U/mg vs 36.5±3.9-U/mg)(P<0.01). In the Ligustrazine treated groups, the levels of MDA decreased and the levels of SOD activity increased compared with the Model group(both P<0.01), but the levels of NO were higher than those of Model group. CONCLUSIONS: Administering ligustrazine during pregnancy can decrease the incidence of fetal IUGR induced by passive smoking and improve the brain development of fetal rats. The effect of ligustrazine works possibly by redressing the unbalance between oxidate and antioxidate system.