To investigate the effect of prenatal stress-induced congenital kidney deficiency constitution on lung development in neonatal rats，and to explore the regulatory mechanism of Zuogui Pills in this process.Methods:Forty female rats were randomly divided into control，model，Zuogui Pills(18.9 g/kg)，and vitamin E(1.44 mg/kg) groups.Except for the control group，all other groups were subjected to compound stress stimulation during pregnancy until delivery.Behavioral assessments included the sucrose preference test and open-field test.Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of glucocorticoids(GC)，glutamic-pyruvic transaminase(GPT)，glutamic oxalacetic transaminase(GOT)，blood urea nitrogen(BUN)，and creatinine(Cr).Hematoxylin and eosin(HE) staining was performed on maternal liver and kidney tissues for safety assessment.The number of pups，body length，body weight，and organ indices of neonatal rats were recorded，and lung development was evaluated via HE staining.Reverse transcription-polymerase chain reaction(RT-PCR) and immunofluorescence were used to detect the expression of vascular endothelial growth factor receptors(VEGFRs).Western blot was employed to examine the expression of proteins in the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway.Results:Compared to the control group，the model group showed significantly reduced maternal body weight during pregnancy，lower litter size，decreased sucrose preference and open-field activity，and elevated GC levels(P<0.05，P<0.01).Zuogui Pills significantly improved these parameters compared to the model group(P<0.05，P<0.01).No significant differences were found in liver and kidney function among groups(P>0.05).Offspring in the model group exhibited reduced body weight，litter size，and lung organ index(P<0.05，P<0.01)，all of which were improved in the Zuogui Pills group(P<0.05，P<0.01).Morphological improvement in lung tissue was observed in the Zuogui Pills group.On the day of birth，neonatal rats in the Zuogui Pills group showed significantly higher mRNA expression of VEGFR1，VEGFR2，and VEGFR3 compared to the model group(P<0.05)，with VEGFR2 mRNA expression exceeding that of VEGFR1 and VEGFR3(P<0.05).VEGFR2 fluorescence signal and the expression levels of JAK2，STAT3，p-JAK2，p-STAT3，and VEGFR2 proteins were also significantly elevated(P<0.05).Conclusion:Zuogui Pills can improve abnormal lung development in offspring rats with congenital kidney deficiency constitution induced by prenatal stress.This effect may be mediated through regulation of the JAK2/STAT3 signaling pathway.