Abstract: OBJECTIVE To evaluate embryo and fetal developmental toxicity of neohesperidin in rats. METHODS According to gestation day 0(GD0) and bodyweight, dams were stratified randomly assigned to 5 groups, as control group(0.5% sodium carboxymethyl cellulose solution), cyclophosphamide group(12 mg·kg^-1), neohesperidin low, middle and high dose group(0.45, 0.9, 1.8 g·kg^-1). Dams were administrated from GD6 to GD15. Bodyweight and food consumption were gained twice and once per week, respectively. At GD20, dams were killed for examination of corpus luteum, implantation, fetal, placenta and so on. RESULTS During study, no abnormal behavior was observed for each group. Compared with the control group, no significant difference was found on bodyweight in each neohesperidin groups, but it decreased in cyclophosphamide group on bodyweight gain. No significant difference was found between control group and 3 neohesperidin groups on corpora luteum, implantation, fetals, placenta and thouse correlative percentage. Uterus weight in cyclophosphamide group decreased. Compared with the control group, body length in neohesperidin high dose group group reduced, body length, tail length, bodyweight and placenta weight decreased in cyclophosphamide group. For examination of external alterations, no change relative to administration in each neohesperidin groups. Changes on anasarca, head, ear, face, limb and digit was found in cyclophosphamide group. For examination of soft tissue alterations, each 1 case ventricle disease was found in neohesperidin groups, 2 cases and 1 case esophagectasia were noted in medium and high dose group, respectively. In cyclophosphamide group, there were changes such as palate, ventricles disease, esophagus, testis and epididymis and so on. For examination of skeletal, the ossification of parietal and sternebra were delayed by neohesperidin as well as ossification might be affected on mandible, cervical and lumbar vertebra, pubis, occipital bone and rib. Cyclophosphamide 12 mg·kg^-1 affected the ossification of skull, vertebra, rib, sternebra and metacarpal. CONCLUSION No toxicity of neohesperidin was found on dams, and no observed adverse effect level(NOAEL) was 1.8 g·kg^-1. Main toxicity of neohesperidin on embry and fetal developmental was the delay of ossification such as parietal and sternebra, it also might affect development of brain and esophageal, NOAEL was lower than 0.45 g·kg^-1.