Objective To study the effect and mechanism of insulin-like growth factor 1 (IGF-1) up regulating miR-155 expression in hypoxic pulmonary hypertension (HPH) of neonatal rats. Methods The HPH model of newborn rats was established. Thirty newborn Wistar rats were divided into model group and nimodipine administration group according to the random number table. Healthy newborn rats were used as the blank control group, 10 rats per group. The mean pulmonary arterial pressure (mPAP) was measured on the 2^nd, 4^th, 8^th and 12^th days of hypoxia in all groups of rats. The serum levels of hypoxia-inducible factor 1α (HIF-1α) and endothelin-1 (ET-1) were measured by ELISA. The lung tissues at the 12^th day of hypoxia were taken and the expression levels of miR-155, HIF-1α and ET-1 were measured. The control group was operated in the same way. Results In the model group, the rats were moving slowly, weak, dim, curled up, depressed, with reduced food intake and weight loss. In the blank control group, the rats were moving quickly, glossy, with normal diet intake and body weight. In the administration group, the rats’ response, body hair, diet intake and weight were between the blank control and model groups. Compared with the control group, the mPAP, HIF-1α and ET-1 of the model group were significantly higher at the 2^nd, 4^th, 8^th and 12^th days of hypoxia ( P < 0. 05), and the mPAP, HIF-1α and ET-1 of the model group were significantly lower at the 2^nd, 4^th, 8^th and 12^th days of hypoxia ( P < 0. 05). In the control group, the lung tissue structure was clear, with intact alveolar wall and no interstitial exudation. In the model group, the pulmonary microvasculature was dilated and congested, the volume of both lungs was increased, with obvious pulmonary edema and inflammatory cell infiltration, and the presence of alveoli of different sizes, and the alveolar septa were obviously thickened. In the administration group, the alveoli were exuded and bleeding, and the capillaries were dilated and congested. Compared with the model group, inflammatory cell infiltration was significantly reduced. Compared with the blank control group, the expression of HIF-1α and ET-1 in the lung tissue of the model group increased significantly ( P < 0. 05), and the expression of miR-155 decreased significantly ( P < 0. 05). Compared with the model group, the expression of HIF-1α and ET-1 in the lung tissue of the drug group decreased significantly ( P < 0. 05), and the expression of miR-155 increased significantly ( P < 0. 05). The target gene of miR-155 and 5’ UTR of HIF-1α were complementary, and miR-155 might regulate the expression of miR-155 in lung tissue by targeting and binding HIF-1α 3’ UTR. Conclusions Hypoxia may be an enhancing factor in inducing the expression of HIF-1α and ET-1, reducing the inhibitory effect of miR-155 on IGF-1R, and causing HPH pulmonary tissue injury. IGF-1 may exert a protective effect on the lung tissue by upregulating the expression of miR-155, reducing the proliferation of IGF-1R cells and promoting apoptosis.