Rationale: Adipose-derived stem cells (ASC) are detectable in the parenchyma and large airways of lungs, and associated with reduced inflammatory infiltration and lung cell death. Objectives: We hypothesized that ASC could ameliorate lung fibrosis induced by repetitive intratracheal bleomycin instillation. Methods: Male 8-week-old C57BL/6J mice (control group n=10, bleomycin only group n=20, bleomycin plus adipose stem cell group n=10) were used. Eighth biweekly dose of bleomycin was injected intratracheally via an intubation procedure at dose of 0.04 units in a total volume of 100μl of sterile saline. Human ASC (6×105 cells) were then administered via intra-peritoneal injection every other week during the latter 2 months of the 4- month bleomycin exposure. Lungs were evaluated for histology, collagen content, and TUNEL staining. Bronchoalveolar lavage (BAL) was performed for cell counts. Measurements and Main Results: Biweekly four-times administrations of ASC were associated with reduced hyperplasia of Clara cells, cuboidal AECs with peri-alveolar ducts inflammatory cells infiltration, septal thickening, enlarged alveoli, and extensive fibrosis in response to repetitively intratracheal of instillation of bleomycin. ASC therapy also revealed to suppress TGF- β level. Conclusions: These results suggest a useful therapeutic effect of ASC on pulmonary fibrosis induced by repetitive bleomycin administration. Further studies are needed to evaluate the efficacy of ASC for the treatment of IPF.