Abstract: Objective To explore the effects of piperine on cell proliferation and migration in angiotensin II (Ang II)-treated rat airway smooth muscle cells (ASMCs). Methods The primary ASMCs of rats were cultured by improved tissue-piece digestion inoculation and trypsin digestion. MTT assay was used to detect the effects of Ang II and Ang II receptor antagonist losartan on cell proliferation activity. After treatment with Ang II and piperine, the cell proliferation activity, the cell cycle distribution and the cell migration were detected by MTT, flow cytometry and Transwell assay, respectively. ERK1/2 inhibitor PD98059 and losartan were then introduced to determine the expression of cyclin D1, MMP-9, p-ERK1/2, ERK1/2, and β-actin proteins by western blot assay. Results After 24 h culture, Ang II treatment dose-dependently promoted the cell proliferative activity in rat ASMCs (P<0.05), and the promotive effect of 10-7 mol/L Ang II was the most significant. Additionally, losartan blocked the Ang II-induced cell proliferative activity in rat ASMCs (P<0.05). 10-7 mol/L Ang II treatment resulted in the elevated cell proliferative activity, higher S phase fraction, increased migrated cell number, and enhanced expression of cyclin D1, MMP-9 and p-ERK1/2 proteins (P<0.05); these effects were dose-dependently reversed by piperine. Both PD98059 and losartan blocked Ang II-induced expression of p-ERK1/2, cyclin D1 and MMP-9 proteins in rat ASMCs. Conclusions Piperine may inhibit Ang II-induced cell proliferation and cell migration via ERK1/2 signaling pathway in rat ASMCs.