OBJECTIVE Novel treatment strategies are needed in the treatment of endometriosis due to limited success rates with the currently available options. As inflammatory and immunological mechanisms have been shown to be involved in the mechanism of the disease, new modalities are likely to emerge. We investigated the effects of infliximab (INF), etanercept (ETA) and letrozole on the regression of experimental endometriosis. STUDY DESIGN In this experimental randomized trial, endometriosis was induced surgically in 44 adult female Sprague-Dawley rats. Establishment of implants was confirmed in 41 animals by a second operation on the 21st day. The rats were then randomly divided into four groups. Group I (n = 10) served as controls. Group II (n = 11) received letrozole (0.18 mg/kg, i.p.), group III (n = 10, i.p.) ETA (2.016 mg/kg, i.p.), and group IV (n = 10) INF (15.12 mg/kg, i.p.) for a second 21-day period. Endometriotic implant size along with peritoneal fluid VEGF level and immunoreactivity were determined before and after the treatment in each group. RESULTS Endometriotic implant size reduced in all treatment groups. The effect of letrozole and ETA on implant size was similar but was significantly better than INF. Level of VEGF in peritoneal fluid did not change in any treatment group but post-treatment VEGF immunoreactivity was found significantly lower in the letrozole treated group. CONCLUSIONS Letrozole and ETA caused a regression on the implant size in experimental endometriosis. The only group with decreased VEGF expression was letrozole.