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IL10 is a pluripotent cytokine that has multiple functions on cells of the immune system. In most cases, IL10 acts as an anti-inflammatory cytokine, dampening the inflammatory response by down-regulating a subset of pro-inflammatory genes induced by TLR signalling. In B cells, IL10 appears to have an additional role enhancing proliferation, differentiation and class-switch recombination required for appropriate responses to antigens. Although the overall mechanism of IL10 action is known, there still remain many gaps in our knowledge. Furthermore, many attempts have failed to utilize IL10 for the treatment of inflammatory conditions. In an effort to understand if miRNAs can shed light on IL10 function, we performed a miRNA array on B cells. We discovered that IL10 can repress key TLR-induced miRNA, such as miR-155, miR-146a and miR-9 as well as up-regulating a range of unknown miRNA. Bioinformatic and experimental analysis revealed that genes such as SHIP1 and Aicda, two well-known miR-155 targets in macrophages and B cells respectively, can be regulated by IL10 through its modulation of miR-155. Analogously, target analysis of specific miRNAs identified in the array, predict that IL10 can regulate a range of previously uncharacterised genes required for its effect on immune cell function. These findings not only highlight a novel mechanism of action for IL10 but suggest that modulation of miRNA may provide an alternative mechanism for the use of IL10 therapeutically.