Objective Lipocalin-2 (LCN-2) is known to act as an antiinflammatory or a proinflammatory mediator depending on cell types. Recently, LCN-2 has been recognized as an adipokine that links obesity and insulin resistance. However, there is no knowledge about the expression mechanism and the role of LCN-2 in pancreatic islet β-cells. Therefore, we examined molecular mechanisms by which proinflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ) induce LCN-2 expression in RINm5F β-cells. Methods RINm5F cells were treated with IL-1β and/or INF-γ. LCN-2 protein and mRNA expressions were examined by Western blot and Northern blot analyses. Transient transfection and luciferase reporter assay was performed to examine the LCN-2 promoter activity. Electrophoretic mobility shift assay (EMSA) was performed to examine the binding of NF-κB to promoter sites of LCN-2. In addition, iNOS and COX-2 expressions were examined by RT-PCR. Results Unlike IL-1β, INF-γ alone did not induce LCN-2 mRNA and protein expression, however, IFN-γ significantly potentiated IL-1β-induced LCN-2 mRNA and protein expression. Meanwhile, INF-γ did not potentiate IL-1β -induced LCN-2 promoter activity, and promoter study using serially deletion constructs showed that NF-κB binding site was a key transcription factor in LCN-2 promoter activity. Also, INF-γ did not potentiate IL-1β-induced the band intensity of DNA-protein complex on NF-κB binding site of LCN-2 promoter. In addition, we found that LCN-2 expression was significantly increased compared with both iNOS and COX-2 under exposure to IL-1β, and that LCN-2 receptor was expressed in islet β-cells RINm5F and INS-1 cells. Conclusion These findings suggest that IFN-γ significantly potentiated IL-1β-induced LCN-2 expression at mRNA and protein level but not at promoter level, and NF-κB binding site was a key factor in IL-1β-induced LCN-2 expression at transcriptional level. In addition, abundant expression of LCN-2 and LCN-2 receptor in β-cells implies that the interaction of LCN-2 and LCN-2 receptor plays a role in β-cell function.