Abstract: Objective To investigate the expression and clinical significance of macrophage inflammatory protein-1α (MIP-1α) and soluble cluster of differentiation 163 (sCD163) in the peripheral blood of patients with active pulmonary tuberculosis (APTB). Methods A total of 265 APTB patients (an APTB group) and 135 latent tuberculosis infection (LTBI) patients (a LTBI group) who were admitted to Department of Infectious Diseases, the 980th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, from April 2020 to January 2024 were enrolled. Meanwhile, another 135 healthy volunteers undergoing routine medical examinations in the same hospital were set as a control group. According to disease severity, APTB patients were further divided into a mild APTB group (n=94), a moderate APTB group (n=120), and a severe APTB group (n=51). Based on prognosis, the patients were further divided into a good prognosis group (n=191) and a poor prognosis group (n=74). Their clinical data were collected and peripheral blood MIP-1α and sCD163 levels were measured by enzyme-linked immunosorbent assay. The relationship between peripheral blood MIP-1α and sCD163 levels and APTB prognosis was analyzed by multivariate unconditional logistic regression. The prediction efficiency of MIP-1α and sCD163 levels for APTB prognosis was assessed by receiver operating characteristic (ROC) curve analysis. Results The levels of peripheral blood MIP-1α and sCD163 in the APTB group were significantly higher than those in the LTBI group and the control gromp (P<0.05). Patients in the severe APTB group showed increased peripheral blood MIP-1α and sCD163 levels compared with those in the moderate and mild APTB groups (P<0.05). The incidence of poor prognosis was 27.92% (74/265). The levels of MIP-1α and sCD163 in the poor prognosis group were significantly higher than those in the good prognosis group (P<0.05). After adjusting for confounding factors, high MIP-1α and high sCD163 levels were identified as independent risk factors for poor prognosis in APTB patients (P<0.05). The area under the ROC curve (AUC) for combined prediction of poor prognosis using MIP-1α and sCD163 was 0.883, which was significantly higher than the AUCs for MIP-1α (0.790) and sCD163 (0.792) alone (P<0.05). Conclusions Elevated levels of MIP-1α and sCD163 in the peripheral blood of APTB patients are associated with disease severity and poor prognosis. Combined detection of peripheral blood MIP-1α and sCD163 provides high predictive efficiency for poor prognosis in APTB patients.