Both baseline pain sensitivity and the response to antinociceptive treatment are sensitive to the animal’s sex and estrous cycle stage. On the other hand, the role of GABA due to GABAB receptor in nociception was investigated. So the aim of present study was to investigate the effect of inter cerebroventicular injection of GABAB receptor agonist (baclofen) and GABAB receptor antagonist (CGP35348) on pain sensitivity during different stages of estrous cycle. Twenty four adult female rats weighting 200-220g were used. Rats were maintained on 12h reversed light/dark cycle, and standard temperature 20±4. Food and water were available ad libitum. Pain sensitivity was evaluated by formalin test. Formalin test was performed by subcutaneous injection 50μl of formalin (2.5%) solution into the hind paw in all stages of estrous cycle. Animal were divided in 4 groups: 1- control (intact animal), 2- sham (received 2μl Artificial cerebrospinal fluid-ACSF), 3- experiment1 (received 2μl of baclofen 4.25 and 8.5μg/rat), 4- experiment2 (received 2μl of CGP35348 3 and 5μg/rat). Data was analyzed by two ways ANOVA measuring. The level of significant was p<0.05. Our data showed that baclofen decrease pain sensitivity in all phases of estrous cycle, but this analgesic effect was high during metestruse and diestruse phase of estrous cycle and low during proestruse and estrus. CGP35348 increased pain sensitivity in all phases of estrous cycle, but this Hyperalgesic effect was low during metestruse and diestruse phase of estrous cycle and high during proestruse and estrus. According to our data GABAergic system can modulate pain sensitivity during estrous cycle.