Background & Aims: Systemic sclerosis is an autoimmune disease of unknown cause and is very difficult to treat. Scleroderma, or systemic sclerosis (SSc), is a multifocal systemic disorder characterized by overactive immune system, systemic inflammation, vascular damage, and tissue fibrosis. The pathogenesis of the disease is mainly based on autoimmune inflammatory processes, systemic vasculopathy and collagen deposition in the skin and internal organs, which leads to tissue fibrosis with severe functional disorders and can be one of the major causes of mortality in these patients. SSc-associated interstitial lung disease (ILD) is a common complication of SSc, which can lead to significant morbidity and mortality. As with other pulmonary fibrotic diseases, damage to epithelial cells, activation of innate and acquired immunity, and activation of fibroblasts may lead to overproduction of the matrix and ulceration of the SSc-ILD. New studies speculate that differentiation and proliferation Myofibroblasts are a key pathological mechanism that increases fibrosis in SSc-ILD. According to EULAR recommendations, cyclophosphamide is the first choice for the treatment of SSc-ILD. Cyclophosphamide acts as a cytotoxic immunosuppressive agent by modulating lymphocyte function, reducing suppression of the inflammatory response and fibrosis. Cyclophosphamide (CYC) is an immunosuppressive alkalizing drug that inhibits the function of lymphocytes in the cellular environment. Moreover, bronchoalveolar lavage and pulmonary function testing are shown. Systemic and intravenous injection of immunosuppressive drugs may be associated with more potential systemic complications. A study published in the New England Journal of Medicine in 2006 found that treatment with cyclophosphamide for one year resulted in significant improvement in lung function and symptoms in patients with SSc-ILD. However, the use of cyclophosphamide is associated with potential side effects, such as increased risk of infection and cancer, and its use should be carefully evaluated on a case-by-case basis.Therefore, choosing the best method of drug administration with the aim of improving the symptoms and skin involvement in patients with systemic sclerosis can be very important and vital. In this study, the effects and immunotherapy of oral cyclophosphamide in the treatment of skin lesions and interstitial lung disease were studied. Methods: The type of study is quasi-experimental, and 21 patients who received cyclophosphamide and had a follow-up of 12 months were included in the study.Twenty-one selected patients included in this retrospective cohort were treated with oral CYC (up to 2 mg/kg/day). Additionally, they received an additional low dose of prednisolone (≤10 mg) for 6 months. Skin score, forced vital capacity (FVC) and diffusion lung capacity for carbon monoxide (DLCO) were assessed as outcome measures. At entry and after 12 months Modified Rodnan Skin Score (MRSS), pulmonary function tests and DLCO have been evaluated. Inclusion criteria include the following: 1- Treatment with cyclophosphamide 2- Follow-up for at least one year from the start of the first dose of the drug 3- The use of oral cyclophosphamide for at least six months 4- Filling the diagnostic criteria of ACR (American College of Rheumatology) 5. Existence Documents related to High-resolution computed tomography (HRCT), PFT and DLCO at the beginning of treatment and 12 months after treatment. Exclusion criteria also included the following: Patients who, in addition to ILD, had pulmonary artery hypertension (PAH) or severe left ventricular failure (EF <50%) were excluded from the study. Patients with normal HRCT and FEV <20% were also excluded from the study, provided that the volume reduction was due to thickening of the skin. The patients received cyclophosphamide at a maximum dose of 2 mg/kg/day (50-100 mg/day) for 12 months. In addition, prednisolone 10-15 mg / day was initially administered for 2 months and then for 10 months at a dose of 5 mg / day. GhRh agonist and oocyte cryopreservation were used for 4 and 8 in 16 patients under 45 years of age, respectively. The major limitations of our study were the small population, and the retrospective nature of the study, which inevitably renders the study unblinded with selection biases. Other limitations included the lack of a comparative control group and the short follow-up period. An advantage of the present study is that all patients completed 1 year of treatment. We also presented all clinical and serological variables in detail, providing sufficient data for future comparative studies. The study was conducted after approval by the Ethics Committee of the University of Iran with the ethics code IRIUMS.FMD.REC.1396.9511288002. Results: The patients’ age at the time of ILD need to treatment/months median (IQR) were 34.0 (29.6–48.5) years, 18 (85%) had female gender, and 8 (38%) had a diffuse subtype of the disease. The mean (SD) FVC percentages obtained at baseline 59.5 ±10.7 and post-treatment 63.1 ± 16.2 with mean difference 2.9 ± 11.5, p=0.19. DLCO% in CYC treated patients at base was 67.7 ± 27.5 and post treatment was 60.0 ±22.9 with a mean difference of −8.0 ± 23.7 (p = 0.12). Following 12 months of treatment mean difference of changes in MRSS was −1.4 ± 4.5 in CYC-treated patients. In the twelfth month, 5 out of 21 patients showed improvement, while 14 patients had stable FVC. Among the patients, only one patient showed improvement in DLCO and 14 patients had stable DLCO. The non-significance of P indicates no change in the parameters and prevention of deterioration of the patient's condition in terms of the investigated parameters following the intervention. After one year of treatment with CYC, two patients showed symptoms of leukopenia, which led to a temporary reduction in the dose of the received drug to improve the condition. Conclusion: Based on our findings, the use of cyclophosphamide as an immunosuppressive drug can prevent the deterioration of patients with SSc-ILD in terms of FVC, DLCO, and MRSS factors. [ABSTRACT FROM AUTHOR]