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Background The renin-angiotensin system plays a key role in the regulation of blood pressure following hemorrhage and shock. Recent studies also suggest renin-angiotensin system regulates inflammatory mediator production although the amechanism is largely unknown. This purpose of the study was to examine the effect of angiotensin II on macrophage (MO) IL-6 messenger RNA (mRNA) expression induced by lipopolysaccharide (LPS) and on the alterations in the calcium influx. Methods J774A.1 cells, a mouse MO cell line, were exposed to E. coli LPS (1 or 10 μg/ml) in the presence of angiotensin II (10 nM to 1 μM). IL-6 mRNA expression was determined by the reverse transcription polymerase chain reaction technique. IL-6 protein production was measured by ELISA. To examine the involvement of calcium signaling in IL-6 mRNA expression, MO were exposed to various calcium agonists and antagonists in the presence of LPS stimulation. Changes of intracellular [Ca 2+ ] by LPS stimulation and angiotensin II treatment were determined by a fura-2 fluorescence ratio method. Results LPS stimulation increased MO IL-6 mRNA expression, which was inhibited by Angiotensin II in a dose-dependent fashion. Both thapsigargin and A23187 augmented the IL-6 mRNA levels induced by LPS stimulation, but only thapsigargin was able to induce IL-6 mRNA directly. TMB-8 but not verapamil inhibited LPS-stimulated MO IL-6 mRNA. Finally, angiotensin II significantly altered the changes in intracellular [Ca 2+ ] levels induced by LPS stimulation by reducing both the peak and slope of calcium spikes. Conclusions Our data show that calcium signaling is closely related to IL-6 mRNA expression. Angiotensin II inhibits IL-6 mRNA expression of LPS-stimulated MO. The inhibitory effects of angiotensin II appear, at least in part, to be mediated through down regulating calcium dependent pathways.