Hydrogen sulfide (H2S) is an endogenous inflammatory mediator produced by the activity of cystathionine γ-lyase (CSE) in mammals. Macrophages are a key element of the immune system and play a crucial role in inflammation. To determine the role of H2S and macrophages in inflammation, we investigated the expression of CSE in human primary macrophages. Our results show that H2S is produced by the activity of CSE in these cells. To investigate the role of common signalling pathway in biosynthesis of CSE in human primary macrophages, specific inhibitors were used to block NF-κB, ERK, p38 and JNK. Inhibition of NF-κB, ERK significantly reduced levels of CSE gene and protein expression in these cells but inhibition of JNK and p38 did not have an inhibitory effect on the expression of CSE gene in macrophages. Inhibition of NF-κB and ERK prevented the effect of LPS on H2S synthesizing activity in human primary macrophages. These data showed that H2S acts as an inflammatory mediator via NF-κB/ERK pathway in macrophages.