Purpose: The nitric oxide (NO) release by inducible nitric oxide synthase (iNOS) is the key events in macrophage response to lipopolysaccharide (LPS) which is suggested to be a crucial mediator for inflammatory and innate immune responses. NO is an important mediator involved in many host defense action and may also lead to a harmful host response to bacterial infection. However, given the importance of iNOS in a variety of pathophysiological conditions, control of its expression and signaling events in response to LPS has been the subject of considerable investigation. Materials and Methods: The Raw264.7 macrophage cell line was used to observe LPS-stimulated iNOS expression. The expression of iNOS is observed by Western blot analysis and real-time RT-PCR. Protein kinase C $(PKC)-{alpha}$ overexpressing Raw264.7 cells are established to determine the involvement of $PKC-{alpha}$ in LPS-mediated iNOS expression. $NF-{kappa}B$ activity is measured by $I{kappa}B{alpha}$ degradation and $NF-{kappa}B$ luciferase activity assay. Results: We found that various PKC isozymes regulate LPS-induced iNOS expression at the transcriptional and translational levels. The involvement of $PKC-{alpha}$ in LPS-mediated iNOS induction was further confirmed by increased iNOS expression in $PKC-{alpha}$ overexpressing cells. $NF-{kappa}B$ dependent transactivation by LPS was observed and $PKC-{alpha}$ specific inhibitory peptide abolished this activation, indicating that $NF-{kappa}B$ activation is dependent on $PKC-{alpha}$. Conclusion: Our data suggests that $PKC-{alpha}$ is involved in LPS-mediated iNOS expression and that its downstream target is $NF-{kappa}B$. Although $PKC-{alpha}$ is a crucial mediator in the iNOS regulation, other PKC isozymes may contribute LPS-stimulated iNOS expression. This finding is needed to be elucidated in further study.