Abstract： Objective To study the destructive effects of the membrane lipid microdomain with methyl-β-cyclodextrin (MβCD) on the proliferation, transdifferentiation and cell cycle of type Ⅱ alveolar epithelial cell (AEC Ⅱ ). Methods The membrane lipid microdomain of AEC Ⅱ was destroyed by MβCD (MβCD interference group) in vitro, and then cultured with DMEM as control. Cell number was counted with hernacytometer; the proliferation rate was measured by methyl thiazolyl tetrazolium (MTT); flow cytometry was used to assay the cell cycle. The expressions of AEC Ⅱ -specific surfactant protein-C (SP-C)and AEC Ⅰ-specific aquaporin-5 (AQP5) were detected by immunofluorescence and Western blotting analyses. Results Compared with control group, cell number and the cell proliferation was decreased in MβCD interference group at 24, 48 and 72 hours after interaction [cell numbers (× 106/ml) : 2. 74±0. 56 vs.8. 05±0. 92, 4. 45±0. 68 vs. 10. 52±0. 81, 7.82±0. 59 vs. 11.39±0. 81; MTT results (A value) : 0. 25±0. 20 vs. 0. 45±0. 02, 0. 35±0.03 vs. 0. 54±0. 28, 0. 48±0. 04 vs. 0. 59±0. 05, all P＜0. 01]. MβCD could increase the percentage of cells in G0/G1 phases and decreased the percentage in S phases at 24 hours [G0/G1phases: (60. 06±1.65)% vs. (43.43±3. 59)% ; S phases: (16. 20±2.17)% vs. (34. 07±2. 63)%, both P＜0. 05]. Incubation of AEC Ⅱ with MβCD resulted in up-regulation of the expression of SP-C (0. 54±0. 04vs. 0. 47±0. 03, 0. 19±0. 03 vs. 0.06±0. 02) and down-regulation of AQP5 (0. 30±0. 04 vs. 0. 43±0. 06,0. 39±0. 04 vs. 0. 59±0. 04) at 48 hours and 72 hours after interaction (P＜0. 05 or P＜0. 01). Conclusion The destruction of membrane lipid microdomain by the MβCD can inhibi± proliferation and transdifferentiation of AEC Ⅱ , and induce cell cycle arrest in G1 phase.