Backgrounds <p>Hard metal lung disease (HMLD) is an occupational disease caused by exposure to hard metal (HM) dust. We explored TGF-β1, TGF-β2 and KL-6 as potential biomarkers for HMLD by examining their levels in bronchoalveolar lavage fluid (BALF) and serum.</p> Methods <p>Forty-eight female Sprague-Dawley rats were divided into hard metal (HM) and normal control (NC) groups. The HM group was exposed to tungsten carbide-cobalt dust (WC-Co) dust via intratracheal instillation. Cytokine levels in BALF and serum were measured at 4-, 8-, and 12-weeks. Lung changes were assessed by micro-CT and histopathology.</p> Results <p>At 4-, 8-, and 12-weeks, the micro-CT showed ground glass opacities, diffuse ground-glass nodules, and scattered ground glass opacities in both lungs of HM group rats, while the pathological tissue found inflammatory cell infiltration, a large number of multinucleated giant cells, and inflammatory cell infiltration, respectively. TGF-β2 levels in BALF were significantly higher in the HM group at 8 and 12 weeks, while serum TGF-β2 levels were lower. KL-6 levels in BALF were elevated in the HM group at 12 weeks, but serum KL-6 levels were lower at 8 weeks.</p> Conclusions <p>TGF-β2 and KL-6 levels in BALF and serum demonstrate dynamic changes associated with HMLD progression and may serve as potential biomarkers for diagnosis and monitoring. Further studies are needed to explore the underlying mechanisms.</p>