Background: IPF is defined as a specific form of chronic fibrosing interstitial pneumonia limited to the lung, with the histopathology of UIP on surgical lung biopsy. IPF is a devastating disease, with a 5 year survival rate of only 20-30% following diagnosis. The most common cause of death in people with IPF is progression of their underlying lung disease. The current promise of the use of adult stem cells for tissue regeneration and the belief that once irreversibly damaged tissue could be restored to a normal functional capacity using stem cell based therapy, suggests a novel approach for treatment of diverse chronic diseases including pulmonary fibrosis. Aim of the work: to demonstrate the safety of bone marrow derived hMSCs administration during short and longer term follow up and to study the potential curative effect of bronchoscopic or intravenous administration of cultured autologous bone marrow derived hMSCs in IPF patients. Subjects and methods: the study included two groups; target population and control group. The target population included 13 IPF patients who received stem cell therapy, subdivided into 3 subgroups: Subgroup I (cases who received stem cells by bronchoscopic administration); Subgroup II (cases who received stem cells by intravenous administration only) and Subgroup IC (cases who received stem cells by bronchoscopic followed by intravenous administration after 6 months). The control group included 16 IPF patients who received the conventional therapy. They were subjected to written informed consent, demographic data acquisition, full history taking, full clinical examination, ABG with calculation of alveolar arterial oxygen gradient, PFTs, 6MWT, HRCT scan and echocardiography. B.M aspirate was done for the target population to obtain autologous MSCs, then culture of these cells and its administration to the target population. Results: Subgroup (I) showed a statistically significant improvement of PO2, SO2 and P(A-a) oxygen gradient compared to the control group. Subgroup (II) showed an observed improvement of the PaO2, SO2, P(A-a) oxygen gradient, FVC%, FEV1%, FEF25-75% and 6MWD compared to the control group. Subgroup (IC) showed an observed improvement in HRCT fibrosis scores and 6MWD compared to the control group. Regarding changes by time in the target population subgroups, Subgroup (I) showed statistically significant increase in PO2 and SO2 at 1, 3 and 6 months during the course of follow up compared to the baseline data. Subgroup (II) showed an observed improvement in PO2, SO2, P(A-a) oxygen gradient, FVC% and FEV1% compared to the baseline data. Subgroup (IC), showed an observed increase in the mean value of FEF25-75% compared to the baseline data. Conclusion: This work forms the basis for future clinical trials and mechanistic studies aimed at establishing the therapeutic possibility of administration of BM derived hMSCs in IPF patients. Translation of the disease pathogenesis into a group of clinical studies will bring us closer to our real goal of improving patients survival and ultimately curing disease so IPF patients may someday breathe more easily.