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Purpose: Keloids are benign fibroproliferative disorders characterized by the massive proliferation of fibroblasts. Fibroblast activation plays a key role in the invasive growth of keloids. Therefore, a prospective pilot study was conducted to explore the value of 68 Ga-FAPI-04 PET/CT in the assessment of keloids activity., Patients and Methods: Twenty-five patients with keloid were enrolled to conduct 68 Ga-FAPI-04 PET/CT. All patients accepted surgery to remove part of the lesions within 1 week. SUV mean and SUV max were measured for semiquantitative analysis and compared with the Vancouver Scar Scale, Laser Speckle Contrast Imaging, pathology, and immunohistochemical stains., Results: A total of 123 lesions were detected in 25 patients, most of which were distributed in the anterior chest wall. The 68 Ga-FAPI-04 uptake was significantly different at different sites ( P < 0.0001). There was uptake heterogeneity within the keloid lesions, and a significant difference was found between the edge and center of some large lesions. The SUV max of 68 Ga-FAPI-04 showed significantly correlation with the Vancouver Scar Scale ( r = 0.565, P < 0.0001) moderately and the Laser Speckle Contrast Imaging parameters mildly. The SUV max of 68 Ga-FAPI-04 had a moderate correlation with FAPI expression ( r = 0.520, P = 0.022). Moreover, collagen, fibroblast activator protein, and Ki-67 expression were found higher at the edges of keloid tissue than in the center., Conclusions: 68 Ga-FAPI-04 PET/CT can reflect the distribution characteristics of activated fibroblasts in keloid tissue and may provide a novel method for keloid evaluation for further fibroblast-related therapies., Competing Interests: Conflicts of interest and sources of funding: None of the authors have any conflicts of interest or relevant financial activities to disclose. This study was supported by the National High-Level Hospital Clinical Research Funding (2022-PUMCH-C-004, 2022-PUMCH-D-002, 2022-PUMCH-B-041, 2022-PUMCH-A-210, and 2022-PUMCH-C-025), Chinese Academy of Medical Science Innovation Fund for Medical Sciences (2022-I2M-2-002, 2021-I2M-1-016, 2022-I2M-C&T-A-008), Beijing Natural Science Foundation (M22035), and the National Natural Science Foundation of China (82272046)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)