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High-resolution computed tomography (HRCT) is important for diagnosing interstitial lung disease (ILD) in inflammatory rheumatic disease (IRD) patients. However, visual ILD assessment via HRCT often has high inter-reader variability. Artificial intelligence (AI)-based techniques for quantitative image analysis promise more accurate diagnostic and prognostic information. This study evaluated the reliability of artificial intelligence-based quantification of pulmonary HRCT (AIqpHRCT) in IRD-ILD patients and verified IRD-ILD quantification using AIqpHRCT in the clinical setting. Reproducibility of AIqpHRCT was verified for each typical HRCT pattern (ground-glass opacity [GGO], non-specific interstitial pneumonia [NSIP], usual interstitial pneumonia [UIP], granuloma). Additional, 50 HRCT datasets from 50 IRD-ILD patients using AIqpHRCT were analysed and correlated with clinical data and pulmonary lung function parameters. AIqpHRCT presented 100% agreement (coefficient of variation = 0.00%, intraclass correlation coefficient = 1.000) regarding the detection of the different HRCT pattern. Furthermore, AIqpHRCT data showed an increase of ILD from 10.7 ± 28.3% (median = 1.3%) in GGO to 18.9 ± 12.4% (median = 18.0%) in UIP pattern. The extent of fibrosis negatively correlated with FVC (ρ=-0.501), TLC (ρ=-0.622), and DLCO (ρ=-0.693) (p < 0.001). GGO measured by AIqpHRCT also significant negatively correlated with DLCO (ρ=-0.699), TLC (ρ=-0.580) and FVC (ρ=-0.423). For the first time, the study demonstrates that AIpqHRCT provides a highly reliable method for quantifying lung parenchymal changes in HRCT images of IRD-ILD patients. Further, the AIqpHRCT method revealed significant correlations between the extent of ILD and lung function parameters. This highlights the potential of AIpqHRCT in enhancing the accuracy of ILD diagnosis and prognosis in clinical settings, ultimately improving patient management and outcomes., (© 2024. The Author(s).)