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Our previous study has found that CGRP inhibited proliferation of PASMCs induced by hypoxia via inactivation of ERK1/2 signal pathway.Studies have revealed that the ERK1/2 signal pathway was involved in proliferation and activation of lung fibroblasts.We also found that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway.Whether ERK 1/2/eIF3a signal pathway is involved in CGRP-mediated pathogenesis of bleomycin-induced pulmonary fibrosis remains unknown.Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats.Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry.The expression/level of CGRP,TGF-β1, eIF3a, ERK1/2, α-SMA, collagen Ⅰ and collagen Ⅲ was analyzed by radioimmunoassay, immunohistochemisty ,ELISA, real-time PCR or western blot.Sensory CGRP depletion by capsaicin exacerbated hypoxia-induced pulmonary fibrosis in rats, as shown by a significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, accompanied with increased expression of TGF-β1, eIF3a,phosphorylated ERK1/2, α-SMA, collagen Ⅰ and collagen Ⅲ.Exogenous application of CGRP significantly inhibited TGF-β1-induced proliferation and differentiation of pulmonary fibroblastsconcomitantly with decreased expression of eIF3a, phosphorylated ERK1/2,α-SMA, collagen Ⅰ and collagen Ⅲ.These effects of CGRP were abolished in the presence of CGRP8-37.These results suggest that endogenous CGRP is related to the development of pulmonary fibrosis induced by bleomycin, and the inhibitory effect of CGRP on proliferation of lung fibroblasts involves the ERK 1/2/eIF3a signaling pathway.