Aim: To study the protective effects of a triptolide-derived, novel compound,(5R)-5-hydroxytriptolide (LLDT-8), on bleomycin-induced lung fibrosis. Methods:C57BL/6 mice received an intratracheal injection of bleomycin and were then treated with LLDT-8 (0.5, 1, 2 mg/kg, ip) once daily for 7 or 14 consecutive days. The body weight loss and lung index augmentation was observed; the inflammatory re-sponse including differential cells counts of neutrophils, macrophages, and lym-phocytes in the bronchoalveolar lavage fluid (BALF), superoxide dismutase (SOD),and malondialdehyde (MDA) level in the lung homogenates was detected, and the fibrosis extent was evaluated by hydroxyproline content and histopathologi-cal changes in the lungs. In addition, the pro-inflammatory and pro-fibrotic cytokines, tumor necrosis factor-ix (TNF-α), interleukin-4 (IL-4), and transforming growth factor-ix (TGF-α) production in the lungs were measured. Results: LLDT-8alleviated the body weight loss and lung index increase caused by bleomycin,reduced neutrophils and lymphocytes in the BALF, promoted SOD activity,decreased MDA production, and inhibited the hydroxyproline level and the amelio-ration of lung tissue histological damage. Moreover, LLDT-8 suppressed TNF-α,IL-4, and TGF-β production in the lung homogenates. Conclusion: LLDT-8 showed protective effects against bleomycin-induced lung fibrosis, and the results suggested the potential role of LLDT-8 in the treatment of this disease.