Aim Macrophage migration inhibitory factor (MIF) is a cytokine whose expression is elevated in endometriotic tissue from women with the disease but the functional role of this factor in the pathogenesis of the disease is uncertain. The objective of the current study was to examine the role of MIF in the pathogenesis of endometriosis. Method Experimental endometriosis was induced in mice and the ability of the MIF antagonist, ISO-1, to reduce endometriotic implant size was assessed. Results Administration of ISO-1 resulted in a significant reduction in implant size and vascularity (as assessed by Flk1 mRNA expression) which was not associated with an alteration in the reproductive cycle. Conclusion These data suggest that inhibition of MIF activity is associated with a significant reduction in endometriotic implant size and leads us to speculate that a similar approach of targeting MIF may prove useful in treating endometriosis in humans.