Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains as a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon-gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically or not confirmed cases) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB; n = 25) patients. The levels of IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IP-10, TGF-β1, and ADA were determined using cytometric bead assay, ELISA or biochemical tests. IFN-γ, IP-10, TNF, TGF-β, and ADA quantified in PF showed significantly higher concentrations in PlTB patients when compared to nTB. When blood and PF were compared, we have identified significantly higher concentrations of IL-6 and IL-10 in PF, in both groups. TGF-β, solely, showed significantly increased levels in PF and blood from PlTB when both clinical specimens were compared to nTB patients. Principal components analysis (PCA) revealed a T helper type 1 (Th1) pattern mainly attributed to higher levels of IP-10, IFN-γ, TGF-β, and TNF in pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases rather than other causes of exudative effusion, commonly considered in the differential diagnosis of PlTB.