Objective To observe the ultrastructure changes of brain of the late trimester of fetal rats via transumbilical vein injection using contrast-enhanced ultrasonography.Methods The forty pregnant rats in the late trimester were divided into four experimental groups randomly.After being successfully punctured in the umbilical vein,two fetus was randomly chosen from maternal uterus with injection contrast agent SonoVue or normal saline solution(20 fetus/each group).Group A as control group with injection of normal saline solution(120 μl/kg);group B as low dose group with injection of SonoVue 0.014 mg/kg(120μl/kg,0.118 ng/ml);group C as media dose group with injection of SonoVue 0.14 mg/kg(120 μd/kg,1.18mg/ml)and group D as high dose group with injection of SonoVue 1.4 mg/kg(120 μl/kg,11.8 mg/ml).After observing the process of every contrast-enhanced ultrasonographic examination,tissue slices of brain of these fetus were made for electronmicroscope investigation.Results ①There was no enhancement in the fetus and placenta in group A.Enhancement couldn't be clearly seen in group B because of fast wash-out contrast agent.On the contrary,the fetus and placenta enhancement in turn could be seen in group C and group D.Enhancement never be seen in maternal uterus and uterine outside.②There was no significant difference of ultrastructure changes of the fetal brain tissues in group A and group B with electronmicroscope.Different degree rough endoplasmic reticulum enlargement,mitochondria swelling,endothelial cell injury,glycogen deposition and vacuolization in the brain cells were found in group C and group D,and the value of contrast between the two groups was significantly different(P＜0.05).Conclusions It is decreasd gradually effects to perform transumbilical vein contrast enhanced ultrasonography with reducing gradually dose for the late trimester of fetal rats,but enhancement has been invisible in the low dose group.