Monocytes and macrophages are critical cellular mediators of inflammation. However, aberrant activation of these cells contributes to the pathology of acute (for example septic shock) and chronic (for example rheumatoid arthritis) inflammatory diseases. These cell types express an extensive repertoire of G-Protein Coupled Receptors (GPCRs), which are widely targeted in drug discovery. Novel macrophage-expressed GPCRs are likely to impact on inflammatory and immune responses and hence represent targets for development of novel therapeutics. This thesis focused on identifying GPCRs and GPCR signalling molecules expressed by macrophages and investigating their function in this lineage. In Chapter 3 of this thesis, a systematic micro-array analysis of primary mouse macrophages compared to other cell populations was performed to identify GPCRs that are enriched in macrophages. The P2Y family of GPCRs were identified as being highly expressed and/or regulated in macrophages, and the regulated expression of two P2Y family members (P2RY5 and P2RY6) was further investigated in this chapter. Expression profiling was also used to identify macrophageexpressed GPCR signalling molecules, and Chapter 4 focused on the expression and function of one of these, beta-arrestin (ARRB) 2. The macrophage-enriched expression of ARRB2 was confirmed at the mRNA and protein level, and its regulation by inflammatory stimuli in macrophages was also investigated. Given that ARRB2 is a key regulator of GPCR signalling and has also recently emerged as regulator of Toll-like Receptor (TLR) signalling, further research focused on this signalling molecule in an attempt to identify novel functions in macrophages. By expression profiling of ARRB2 deficient BMM, and through the use of a novel cell permeable peptide antagonist of ARRB2, this signalling molecule was identified as a critical regulator of basal and LPS-inducible complement C1q expression. Furthermore, ARRB2 limited factor-independent survival and regulated activation of ERK-1/2 and JNK MAPK in macrophages. Chapter 5 documented a defect in LPS-inducible expression of the histone deacetylase, Hdac1 in ARRB2-/- macrophages, and explored the consequences of this on macrophage inflammatory pathways. Thus Chapters 4 and 5 identified novel pathways by which ARRB2 positively regulates LPS-inducible gene expression in macrophages. Given that loss of C1q expression is associated with systemic lupus erythematosus (SLE) and that HDAC1 is a feedback regulator of macrophage activation, understanding the mechanisms by which ARRB2 regulates the expression of these genes will provide further insight into inflammatory disease processes.