Objective: Long-term clinical application has demonstrated that Qibai Pingfei capsule possesses a remarkable therapeutic effect on chronic obstructive pulmonary disease.To observe the effect of Qibai Pingfei capsule medicated serum(QBPF)on the proliferation of rat pulmonary arterial smooth muscle cells(PASMCs)under hypoxia and the key molecular mechanism on Ca2+/calcineurin/nuclear factor of activated T cells(NFATc3)signal pathway.Methods: Qibai Pingfei capsule was provided to rats via continuous gavage for 10 days to obtain QBPF.Primary rat PASMCs were cultured using tissue explants adherent method.Methyl thiazolyl tetrazolium(MTT)was used to detect the effect of QBPF on PASMCs proliferation under hypoxia.Laser scanning confocal microscopy was used to detect the changes in [Ca2+]i in PASMC-loaded Fluo-3-AM.RT-qPCR and Western blot were applied to detect the transcription and protein expression levels of Calcineurin and NFATc3 gene in PASMCs.Results: Compared with normoxia group,PASCMs proliferated at 12,24,48,and 72h under hypoxia,and QBPF at a concentration of 5%,10%,and 20%could inhibit hypoxia-induced proliferation of PASCMs at different degrees.The inhibitory effect was most significant in the 20%QBPF group under hypoxia for 24 h.[Ca2+]i in PASCMs under hypoxia was increased,and [Ca2+]i could be significantly decreased when co-incubated with QBPF at 5%,10%,and 20%.Compared with the normoxia group,the mRNA and protein expression levels of calcineurin and NFATc3 in PASCMs induced by hypoxia were up-regulated.The intervention of QBPF could significantly down-regulate mRNA and protein expression levels of calcineurin and NFATc3 in PASCMs.Conclusion: QBPF could effectively inhibit hypoxia-induced proliferation of PASCMs through downregulation of the key molecular expression via Ca2+/calcineurin/NFATc3 pathway.