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Yi-Ran Han,1,* Tian-Hao Wang,2,* Wen-Ping Gong,3,* Jian-Qin Liang,1 Hui-Ru An1 1Department of Tuberculosis, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, People’s Republic of China; 2Department of Emergency, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, People’s Republic of China; 3Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute for Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of Chinese PLA General Hospital in China, Beijing, 100091, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui-Ru An; Jian-Qin Liang, Department of Tuberculosis, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, No. 17 of Heishanhu Road, Haidian District, Beijing, 100091, People’s Republic of China, Tel +86 10 66775098, Email anhuiru25@outlook.com; wliangjianqin@126.comObjective: To make a systematic evaluation of the clinical efficacy of thymopentin combined with antituberculous drugs in treating drug-resistant pulmonary TB (PTB).Methods: Relevant studies were retrieved from PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database, CNKI, and Wanfang Database. STATA software was used to evaluate the differences in focal absorption rate, the time to cough symptom remission, sputum culture-negative rate, CD3+ T, CD4+ T, and CD8+ T cell levels after treatment.Results: A total of 23 randomized controlled trials literature involving 2031 cases were included. Meta-analysis revealed that compared with conventional therapy, the sputum culture-negative rate was significantly increased after 2– 3 months and 6– 9 months of treatment and the whole course of combined thymopentin treatment. The risk ratio (RR, 95% CI) was 1.44 (1.26– 1.64), 1.47 (1.21– 1.78), and 1.27 (1.18– 1.36), respectively. In the combined thymopentin treatment group, the focal absorption rate was higher, with RR (95% CI) = 1.36 (1.25– 1.47), the time of cough remission was shortened, with WMD (95% CI) =− 9.46d (− 10.36,− 8.57) and the differences were all statistically significant. Combined thymopentin therapy could effectively improve the levels of CD3+ T and CD4+ T lymphocytes in patients with drug-resistant PTB after 2– 3 months, 6– 9 months of treatment. The WMD (95% CI) were 9.96% (7.84, 12.08), 4.68% (2.90, 6.47) and 10.26% (7.81, 12.71), 7.21% (6.28, 8.15), respectively, and could also reduce the level of CD8+ T lymphocytes after 2– 3 months and 6– 9 months of treatment. The WMD (95% CI) were − 4.06% (− 4.96, − 3.13), − 3.52%, (− 4.07,− 2.98), respectively, and the differences were all statistically significant.Conclusion: Thymopentin adjuvant treatment for drug-resistant PTB can promote the therapeutic effect and improve the immune indexes in patients with drug-resistant PTB.Keywords: thymopentin, drug resistance, pulmonary TB, immunity, meta-analysis