To assess the effectiveness of cyclophosphamide in the management of scleroderma-related interstitial lung disease (ILD). In this systematic review study, the primary outcome measures were change in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (D(L)CO) of the patients after 6 and 12 months. To assess the effect of cyclophosphamide on early stage of ILD, alveolitis, in SSc patients, we selected the studies that used the BAL findings or HRCT or recent deterioration of PFT with minimal chest X-ray finding in early stage of disease as diagnosis of alveolitis. A sensitive systematic search strategy was used to find all relevant studies. Finally, 17 trials were included in the analysis that was performed using STATA. (Version 8) and Review Manager (version 4.1; MetaView version 4.1) softwares. Results from 10 studies were pooled for the outcome variable of FVC after 12 months. The summary WMD (random effects) was 2.45 (95% CI, 0.760-4.149 P = 0.005), which means that cyclophosphamide was able to prevent deterioration of FVC after 12 months. In pooled data of 13 studies, about DLCO after 12 months WMD (random effects) was 2.003 2.96 (95% CI, -0.228 to 6.159 P = 0.069), which means that cyclophosphamide was not able to prevent deterioration of D(L)CO after 12 months. If we considered clinically sensible improvement as absolute value ≥10% in DLCO and VC, then result of treatment with cyclophosphamide treatment in scleroderma patients with ILD was not significant.