Leptin is a 16 kDa protein which consists of 167 amino acids. Leptin is considered as one of the adipokines, secreted by white adipocytes, and is the product of the obese (ob) gene. Recently, leptin is recognized as the immuno-stimulator which belongs to the same class of long chain helical cytokines such as interleukin (IL)-6. Leptin is related to the immune responses evoked by Mycobacterium tuberculosis infection. Thus, studies of association between immunomolecules including leptin and tuberculosis may contribute to provide an essential solution regulating adverse immune responses in several mycobacterial diseases. Leptin has a multifunctional role in the secretion of acute-phase cytokines including IL-1beta and tumor-necrosis factor-alpha (TNF-alpha), and links to T helper 1 (Th1) immune response. Moreover, the binding of leptin to leptin receptor (LepR) is important in that this binding involves janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. In addition, the activation of LepR mediates extra-cellular signal-regulated kinase (ERK) and phosphoinositide 3 kinase (PI3K) pathways. Furthermore, many studies suggest that leptin may play a critical role in respiratory diseases including chronic obstructive pulmonary disease (COPD) and asthma as well as tuberculosis. These findings indicate that leptin is one of the important regulators for immune responses in respiratory diseases. We herein discuss the multifunctional role of leptin in mycobacterial lung disease, especially focusing on the related pathway to immune responses.