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Initially, H<jats:sub>2<\/jats:sub>S was recognized by its roles in neuronal activity and vascular relaxation, which makes it an important molecule involved in paracrine signalling pathways. Recently, the immune regulatory function of gasotransmitters, H<jats:sub>2<\/jats:sub>S in particular, is increasingly being appreciated. Endogenous H<jats:sub>2<\/jats:sub>S level has been linked to macrophage activation, polarization and inflammasome formation. Mechanistically, H<jats:sub>2<\/jats:sub>S\u2010induced protein S\u2010sulphydration suppresses several inflammatory pathways including NF\u2010\u03baB and JNK signalling. Moreover, H<jats:sub>2<\/jats:sub>S serves as a potent cellular redox regulator to modulate epigenetic alterations and to promote mitochondrial biogenesis in macrophages. Here in this review, we intend to summarize the recent advancements of H<jats:sub>2<\/jats:sub>S studies in macrophages, and to discuss with focus on the therapeutic potential of H<jats:sub>2<\/jats:sub>S donors by targeting macrophages. 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