Abstract: In February 2023, a 48-year-old male with cough and expectoration was admitted to the Department of Pulmonary and Critical Care Medicine of Peking University People’s Hospital. CT indicated mediastinal soft-tissue mass under the tracheal carina. Meta-genomics next generation sequencing of mediastinal abscess suggested infection with Tropheryma whipplei, which was positive for periodic acid-Schiff staining. The patient had no history of diarrhea, weight loss, or joint pain. The patient was diagnosed with Whipple’s disease and treated with ceftriaxone followed by trimethoprim-sulfamethoxazole therapy. After 1-year post-discharge therapy, the patieny’s symptoms and general condition improved significantly, and remained to follow.