This study is to explore the activation of the Ca²⁺/CaM/CaN signal pathway in 5-HT-induced  proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-nisoldipine (m-Nis) on this pathway.  PASMCs were cultured with the explant technique.  The proliferation of PASMCs was evaluated by MTT assay.  Confocal microscopy was used to measure the change of Ca²⁺_i.  The mRNA expression of CaM and CaN was evaluated by RT-PCR and the activity of CaN was measured according to   the instruction of kits.  The results of MTT assay suggested that 5-HT (1 μmol·L⁻¹) significantly induced the proliferation of rat PASMCs (P < 0.01), which was inhibited obviously by m-Nis (P < 0.05 or P < 0.01).  Similarly, m-Nis inhibited 5-HT-induced elevation of Ca²⁺_i (P < 0.01).  The mRNA expression of CaM, CaN and the  activation of CaN were also inhibited by m-Nis at different degrees (P < 0.05 or P < 0.01).  Thus, the results of this study suggested that Ca²⁺/CaM/CaN signal pathway played an important role in 5-HT-induced proliferation of rat PASMCs, the inhibition of m-Nis on proliferation of rat PASMCs may be related to the blockage of Ca²⁺/CaM/CaN signal pathway by inhibiting the elevation of Ca²⁺_i.