Long intergenic non-coding RNAs (lincRNAs) are long non-coding transcripts from the intergenic regions of annotated protein-coding genes. lincRNA cyclooxygenase 2 (Cox2) is an early-primary response gene regulated by the NF-kappa B signaling pathway in macrophages. It was found that lincRNACox2 was significantly increased in patients with the Mycobacterium tuberculosis (M. tuberculosis) H37Ra strain infection and macrophages, using reverse transcription-quantitative PCR (RT-qPCR). ELISA, western blotting and RT-qPCR results indicated that the inflammatory response factors tumor necrosis factor-alpha, interferon-gamma, interleukin-6, Cox2 and inducible nitric oxide synthase were significantly increased in H37Ra infected macrophages. In addition, the inflammatory regulating proteins NF-kappa B and Stat3 were significantly increased in H37Ra infected macrophages but decreased in lincRNACox2 knockdown macrophages infected with H37Ra. Moreover, the knockdown of lincRNACox2 increased the apoptotic rate of H37Ra infected macrophages and facilitated the proliferation of H37Ra. Collectively, the present results suggested that lincRNACox2 may be required for the activation of NF-kappa B and Stat3, in order to regulate inflammatory responses involved in resistance to M. tuberculosis infection.