Stress facilitates pain perception and sensitizes pain pathways，but the underlying mechanism is still unclear. The purpose of this study was to investigate whether activation of 5-hydroxytryptamine (5-HT) subtype-3 receptor in the spinal cord contributes to somatic hyperalgesia induced by repeated 3 day forced swim (FS) in the estradiol (E2) replacement rats after ovariectomy (OVx). Somatic sensitivity was assessed by thermal withdrawal latency to radiant heat and mechanical withdrawal threshold to von Frey filaments. The expression of 5-HT3A receptor in the L4-L5 dorsal spinal cord was examined by Western blot. Repeated FS stress reduced the thermal withdrawal latency and mechanical withdrawal threshold, and the presence of E2 exaggerated this hyperalgesia. The expression of 5-HT3A receptor in the L4-L5 dorsal spinal cord increased significantly following repeated FS in E2 replacement rats. Intrathecal injection of 5-HT3 receptor antagonist Y-25130 blocked the somatic hyperalgesia induced by FS stress. These data indicate that 5-HT3 receptor activation through the descending facilitation system contributes to the somatic hyperalgesia evoked by FS stress. The results may provide a new therapeutic avenue for alleviating pain induced by stress.