Objective: Observe and analyze the clinical significance of the differences in the expression levels of sCD163, haptoglobin and cytokines. Methods: 120 patients with tuberculous pleural effusion diagnosed in our hospital from January 2019 to December 2021 were randomly selected as the experimental group. On the other hand, 40 patients with non-tuberculous pleural effusion admitted in the same period were selected as the control group. The expression levels of sCD163, haptoglobin and cytokines were observed and analyzed. Results: The expression levels of sCD163 (?g/mL), haptoglobin (g/L), IL-6 (pg/mL) and IL-12 (pg/mL) of the control group were 31.26 ± 14.12, 32.14 ± 18.79, 401.23 ± 24.36 and 1.32 ± 0.14, respectively. As for the experimental group, the expression levels of sCD163 (?g/mL), haptoglobin (g/L), IL-6 (pg/mL) and IL-12 (pg/mL) were 74.12 ± 14.78, 113.25 ± 19.45, 612.12 ± 36.98 and 4.12 ± 0.56 respectively, and p < 0.05 which shows that the data was statistically significant. Conclusion: The level of inflammatory cytokines in the pleural fluid of tuberculous pleural effusion patients are higher, which can be used for the diagnosis of auxiliary tuberculous pleurisy. Tuberculous pleural effusion patients has a significantly increased expression levels of sCD163 and haptoglobin in the pleural fluid. The combination of sCD163 and haptoglobin in the diagnosis of tuberculous pleural effusion has higher clinical diagnostic value, and sCD163 and haptoglobin are not interfered by inflammatory factors in the diagnosis of tuberculous pleural effusion