Background: Space is a harsh environment that affects the body in many ways. Humans venturing into the environment of space can have negative effects on the body. Objectives: This study focused on the effects of simulated microgravity on beta-endorphin receptor concentration. Methods: Rats (n =16) were divided in two groups (n = 8/group), freely moving (control group) and hindlimb unloading. A rat-tail suspension model was used in experiment groups for 14 days to explore the effect of simulated microgravity on the beta-endorphin receptor concentration in the hippocampus, brain stem, and prefrontal cortex. Results: The results showed that the concentration of beta-endorphin receptor in the brain stem and prefrontal cortex, but not in hippocampus, was significantly higher in hindlimb unloading rats than controls. Conclusions: It is possible that simulated microgravity may increase the beta-endorphin receptor expression in the prefrontal cortex and brain stem in the rat.