Objective:To establish an reliable and stable method of establishing an optimal animal model of lung injury in neonate rat intraperitoneal injection of lipopolysaccharides (LPS). Methods:Pregnant Sprague-Dawley rats on gestation day 18 were randomly divided into the control group and the LPS experimental group. Rats were injected intraperitoneally with 0.5,1.0,1.5,2.0 and 2.5 mg/kg LPS, respectively, in the LPS groups and with equal amount of saline in the control group,and then the mortality and abortion ratio of pregnant rats rate were measured. According to the statistical results,we next selected low mortality doses of LPS (0.9,0.8,0.7,0.6,and 0.5 mg/kg) and intraperitoneally injected to pregnant rats. Lung tissues were collected from neonatal rat at postnatal day 1. The indexes of pathological score and wet/dry weight ratio (W/D) of lung lobes were observed. The mRNA expression of TNF-α and IL-1β,and the TNF- α protein expression in lung tissues were examined. Furthermore,to study the LPS of 0.7 mg/kg dose,the mRNA expression of TNF-α,IL-1β in placental and fetal lung tissues were measured on day 19. The same indexes of neonatal rats lung were also examined on day 1,4 and 7 after natural birth,respectively. Results: ①The mortality and abortion ratios of pregnant rats were decreased gradually with the decreasing LPS doses. When the dosage of LPS was less than 1.0 mg/kg,these two indexes were reduced to below 25%. ②When the dosage of LPS ranged from 0.5 to 1.0 mg/kg,pathological score,W/D score and the mRNA levels of TNF-α,IL-1β were significantly higher than those in the control group under the condition of LPS≥0.7 mg/kg (P < 0.05 ). When the dosage of LPS < 0.7 mg/kg,the above indexes showed no statistical significance (P > 0.05 ). ③When the dosage of LPS = 0.7 mg/kg,the expressions of TNF-α,IL-1β mRNA in placenta and fetal issues increased more obviously (P < 0.05 ) than that in the control group. Compared to the control group,the mRNA expression of TNF-α and IL-1β in lung tissues of neonatal rats on day 1,4,and 7 was significantly increased(all P < 0.05). Conclusion:Intraperitoneal LPS (0.7 mg/kg) given to pregnant SD rats on 18th day of gestation led to lung injury,and pulmonary edema and increase TNF-α and IL-1β in newborn rats,which continued into the 7th day after birth. This is a stable and reliable method to construct the model of lung injury in neonate rat with intrauterine infection.