Diffusion lung capacity for carbon monoxide correlates with HRCT findings in patients with diffuse parenchymal lung disease. Background Diffuse parenchymal lung diseases (DPLDs) affect the alveolar epithelium, pulmonary capillary endothelium, basement membrane, and perivascular and perilymphatic tissues. High-resolution computed tomography (HRCT) of the chest is the gold standard modality for diagnosing DPLD. Pulmonary function tests usually show a restrictive defect in spirometry. Single breath diffusion lung capacity for carbon monoxide (DLCO-SB) technique is used to assess the diffuse parenchymal lung diseases, as there is thickening of the alveolar membrane and diminished total lung capacity due to interstitial processes with severe decline in the transfer factor. The aim of this work was to correlate between Warrick’s HRCT fibrosis score and DLCO-SB in DPLD and to assess the possibility of using DLCO as an only tool to follow up DPLD to avoid repeated radiation exposure of the patients in HRCT chest (decrease need for radiological follow-up) or vice versa. Results This work recruited 89 patients over a period of 10 months duration, 74.2% of them were females. The Warrick’s score, ground-glass opacity, irregular pleural margin, subpleural cyst, honeycombing, and septal and subpleural lines were represented as 96.6%, 70.8%, 55.1%, 49.4%, and 48.3% respectively in HRCT of DPLD. Warrick’s score and its subscores (severity score, extent score, alveolitis score, and fibrosis score) were associated with a highly significant decrease in different pulmonary function indices (FVC, FEV1, TLC, and DLCO) with P value 0.001. A highly significant correlation between DLCO grades and total score grades was found with P value 0.001, and 86.8% of the patients with severe DLCO affection showed severe degree of total fibrosis score. Conclusions Both DLCO-SB and HRCT fibrosis scores were significantly correlated. Lifelong follow-up of function and structure of the lung in DPLD is needed by HRCT and DLCO. In an attempt to minimize repeated radiation exposure and reduce cost, we suggest DLCO to be used alone for longer follow-up periods rather than HRCT chest.