Interleukin 8 (IL-8, CXCL8) is a pro-inflammatory chemokine which attracts neutrophils to sites of inflammation via an activation of the G-protein-coupled receptors, CXCR1 and CXCR2. However, both IL-8 and IL-8 receptors are widely expressed in various tissues and cell types, and have been suggested to be involved in other functions such as angiogenesis, tumor growth, or brain pathology. We examined the expression of IL-8 and IL-8 receptors in highly enriched primary cultures of guinea pig Muller glial cells. Immunoreactivity for CXCL8, CXCR1 and CXCR2 was observed in all cultured Muller cells. The expression of CXCL8 was confirmed by PCR, and the secretion of the CXCL8 protein from Muller cells was revealed by ELISA. Western blots showed prominent bands at approximately 40 kDa by using antibodies specific for human CXCR1 and CXCR2, and the expression of a putative CXCR2 receptor in Muller cells was confirmed by PCR. Furthermore, cultured Muller cells responded to application of recombinant human IL-8 with an increase of the cytosolic Ca(2+) concentration. If supernatants of cultured human retinal pigment epithelium (RPE) cells were applied to the Muller cell cultures, no obvious changes were observed in the CXCL8, CXCR1 and CXCR2 expression but (i) Muller cell proliferation was stimulated, and (ii) there was an increased number of CXCL8-responsive Muller cells and the amplitudes of the evoked calcium responses were enhanced. It is concluded that Muller glial cells may participate in the inflammatory response(s) of the retina during ocular diseases, and that this contribution may be modified by interactions with RPE cells.