Abstract: AIM: To investigate the effects of hypoxia on the expressions of 5-HT1B receptors in rat pulmonary arteries and to explore the mechanism of hypoxic pulmonary hypertension (HPH). METHODS: Forty male Sprague Dawley rats were randomly divided into four groups: normoxia control, 3-week hypoxia, 4-week hypoxia and 6-week hypoxia. The rats in normoxia control remained in a normal environment, whereas rats in 3- , 4- and 6-week hypoxia groups were kept, respectively, in hypoxia chamber for 3, 4 and 6 weeks to establish the HPH animal model. After HPH rats were established, mean pulmonary pressure (mPAP) and right ventricular systolic pressure (RVSP) were recorded by a microcatheter. RV/(LV+S) ratio was calculated to assess right ventricular hypertrophy. 5-HT1B receptor expressions in pulmonary arteries and lung tissues were measured by immunohistochemistry and Western blot analyses. RESULTS: Compared with those in normoxia control group, mPAP, RVSP and RV/(LV+S)% of 3-week hypoxia rats increased significantly (P<0.05), which continued to increase following prolonged hypoxia. Immunohistochemistry showed that 5-HT1B was localized mainly in the intima of pulmonary arteries of normoxia group of rats. Exposed to hypoxia, 5-HT1B receptor increased in the media of rat pulmonary arteries, particularly those bordering the adventitia. More changes were observed in the expressions of 5-HT1B receptor following prolonged hypoxia. Western blot results showed the same changes of 5-HT1B receptor expressions in lung tissues as that of 5-HT1B receptor immunoreactivity in pulmonary arteries. CONCLUSION: Hypoxia induces overexpression of 5-HT1B receptor in pulmonary arteries of HPH rats, which may be one of the underlying mechanisms of 5-HT-induced HPH development.