Objective To systematically evaluate the efficacy and safety of different administration methods of recombinant human endostatin(Endostatin)in the treatment of malignant pleural effusion in non-small cell lung cancer(NSCLC),and to provide more evidence-based bases for the clinical standardization of the use of Endostatin beyond the drug specification.Methods PubMed,The Cochrane Library,Web of Science,Embase,ChiCTR,VIP,CNKI,WanFang,and SinoMed databases were searched by computer for randomized controlled trials(RCT)of Endostatin alone or combined with chemotherapy for malignant pleural effusion in NSCLC.Network Meta-analysis was performed using Stata 14.0 software.Results A total of 50 RCTs involving 3 429 patients were included,covering 5 intervention measures.Network Meta-analysis showed that in terms of clinical effectiveness,there was no statistically significant difference between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip),and Endostatin(thoracic perfusion)and chemotherapeutic drug(thoracic perfusion)(P＞0.05);there were statistically differences between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(thoracic perfusion)[OR=3.44,95％CI(2.29,4.50),P＜0.05],and Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and chemotherapeutic drug(thoracic perfusion)[OR=3.78,95％CI(3.16,4.51),P＜0.05](P＜0.05).The surface under the cumulative ranking curve(SUCRA)showed that Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)＞Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip)＞Endostatin(thoracic perfusion)＞chemotherapeutic drug(thoracic perfusion)＞chemotherapeutic drug(intravenous drip).In terms of adverse effects,such as gastrointestinal reaction,and reduction of white blood cells and platelets,there was no statistically significant difference among the different interventions(P＞0.05).Conclusion Endostatin either by pleural instillation or combined with first-line chemotherapy drugs significantly improves clinical efficacy in malignant pleural effusion in NSCLC,and it is better and safer with thoracic perfusion efficacy.