Objective To determine the effects of retinoic acid (RA) on establishment and growth of endometrial lesions, peritoneal IL-6 and MCP-1 concentrations, and CD38, CD11b, F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of endometriosis. Design Experimental transplantation study using mice. Setting Academic medical center. Animals C57BL/6 recipient mice and syngeneic Green Fluorescent Protein transgenic (GFP+) mice. Intervention(s) Recipient mice were inoculated with GFP+ minced uterine tissue to induce endometriosis and treated with RA (400 nmol/day) or vehicle for 17 days (3 days before to 14 days after tissue injection). Main Outcome Measure(s) Total number of GFP+ implants in recipient mice, number of implants showing visible blood vessels, total volume of established lesions per mouse, concentrations of IL-6 and MCP-1 in peritoneal fluid, expression of CD11b, F4/80 and CD38 on peritoneal macrophages. Results 17 days of RA treatment reduced the number of implants versus controls and decreased the frequency of lesions with vessels. Peritoneal washings in RA-treated animals had lower IL-6 and MCP-1 than controls 3 days after endometrial inoculation and lower levels of IL-6 on day 14 after inoculation. Concomitant with these effects on day 14, CD38, CD11b, and F4/80 were higher on macrophages from RA-treated mice vs. controls. Conclusions RA inhibits the development of endometriotic implants. This effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and enhanced differentiation of peritoneal macrophages.