【Abstract】 Objective To evaluate the clinical application of medical thoracoscopy for the diagnosis of unknown origin pleural effusion. Methods A retrospective review of 301 patients undergoing a thoracoscopic operation was performed. The diagnosis was confirmed by biopsy. Results Of 301 patients by histopathological examination, there were 103 malignant tumor (including 82 adenocarcinoma, 10 squamous carcinoma, 3 glands squamous carcinoma cases, 3 small cell carcinoma, 2 mesothelium cell tumor, 1 signet ring cell carcinoma case, 1 T cell malignant tumor and 1 plasma cell tumor),156 tuberculous pleurisy, 1 fungi infection, 4 non caseating granuloma, 9 fibrinous inflammation and 28 cases Non-confirmed. Diagnosis rate was 907%. Malignant tumor displayed nodules or masses with different size like cauliflower or grape bunch, while tuberculous pleurisy always appeared as diffused pleural congestion and edema, with wide distribution of small miliary nodules and caseous necrosis. 89 cases of postoperative pain needed analgesia. 2 patients had pleural reaction. 3 patients had reexpansion pulmonary edema. Conclusio Medical thoracoscopy with pleural biopsy is a relatively safe method with high diagnostic rate for pleural effusion of unknown origin.