Background Diffuse pulmonary fibrosis is a progressively worsening lung disease that poses a serious threat to human health. Current treatment options are limited and generally ineffective. Objectives This study aimed to investigate the therapeutic effects of GubenYifei-Tang (GB) in a rat model of pneumoconiosis. Materials and Methods We established a chronic pneumoconiosis model in rats through intratracheal injection of silica dust. Subsequently, the rats were randomly assigned to various groups, including the model group (NC group), Hanfangji Masu tablet group (TET group), high-dose GB group (GB-H group), low-dose GB group (GB-L group), and a blank control group comprising 12 normal rats (NC group). We assessed blood biochemical, vascular endothelial function, immunoinflammatory factors, and oxidative stress indices in four rats from each group at the 1st, 3rd, and 6th months of administration. Results Throughout the 6-month administration period, rats in the GB-L and GB-H groups displayed no significant abnormalities in their general condition or body weight. Both high and low doses of GB significantly reduced the respiratory rate and increased the respiratory amplitude of the pneumoconiosis model rats ( p < 0.05). Additionally, they significantly decreased the mean pulmonary arterial pressure of these rats ( p < 0.05). Moreover, we observed noteworthy improvements in blood gas indices and hypoxemia symptoms, including increased pH, decreased arterial partial pressure of carbon dioxide, increased arterial oxygen partial pressure, and arterial oxygen saturation. Compared to the NC group, the model group rats exhibited significantly elevated concentrations of serum transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and interleukin-1 ( p < 0.01). High-dose GB significantly reduced serum levels of TGF-β, TNF-α, and interleukin-10 in rats, while low-dose GB partially improved serum inflammatory factor levels. Additionally, the lung mass index, malondialdehyde (MDA) levels, and hydroxyproline levels were significantly increased in the model group rats compared to the NC group ( p < 0.01), accompanied by decreased superoxide dismutase (SOD) levels. Both high and low doses of GB demonstrated substantial improvements in lung mass index, MDA, SOD, and hydroxyproline levels in rats ( p < 0.05). Conclusion In the rat model of pneumoconiosis, GB exerts a positive therapeutic impact on lung tissue lesions and respiratory function, with its effectiveness being both time- and dose-dependent.