Objective To investigate the effects of BCG ( Bacillus Calmette-Guerin) infection on NKG2D (natural killer group 2, member D) ligands (MICA, MICB, ULBP1 and ULBP2) expressed on macrophages and to further analyze the effects of baicalin on these NKG2D ligands and the cytotoxic activity of NK cells. Methods PMA ( phorbol 12-myristate 13-acetate) was used to induce the differentiation of THP-1 cells into macrophages. The THP-1-derived macrophages were infected with BCG and then treated with baicalin. The expression of MICA, MICB, ULBP1 and ULBP2 at mRNA and protein levels were meas-ured by real-time PCR and Western blot assay. The BCG-infected macrophages were co-cultured with NK cells derived from human PBMC for 4 h. Real-Time Cell Analyzer ( RTCA DP) was used to evaluate the cy-totoxic activity of NK cells. Results The expression of MICA, MICB, ULBP1 and ULBP2 at mRNA level and the expression of MICA and ULBP1 at protein level were upregulated after infecting the macrophages with BCG. The expression of MICA and ULBP1 at mRNA and protein levels and the killing activity of NK cells were significantly enhanced after treating the BCG-infected macrophages with baicalin (1 mg/L) for 72 h. Conclusion BCG infection could induce the expression of NKG2D ligands on human macrophages, but could not effectively active the NK cells. Baicalin could enhance the cytotoxic activity of NK cells by further up-regulating the expression of NKG2D ligands on BCG-infected macrophages.