Objective To investigate the effect of an MST1 / 2 kinase inhibitor on expression of YAP, GAP43,Caspase 3, and GFAP in rats with acute spinal cord contusion ( SCC). Methods A total of 105 adult female SD rats weighing 180 ~ 200 g were used, of which 35 rats were subjected to a laminectomy and no drug injection as the sham operation group, whereas 70 rats were subjected to spinal cord contusion and divided into normal saline and MST1 / 2 inhibitor groups injected with normal saline or 1 mg / kg XMU-MP-1, respectively. Western Blot and immunofluorescence were used to observe YAP, GAP43, Caspase3 and GFAP expression. BBB and inclined plane tests were used to observe motor functions in rats. Results The inclined plane test and BBB scoring showed the scores of the MST1 / 2 inhibitor group were significantly better than those of normal saline group from day 7 to 28 (P< 0. 05). Western Blot showed that YAP expression in the MST1 / 2 inhibitor group was significantly higher than that the normal saline group from day 14. GFAP and Caspase3 expression in the MST1 / 2 inhibitor group was significantly lower than that in the normal saline group from day 14.GAP43 expression was also observed in the MST1 / 2 inhibitor group from day 14. These differences were statistically significant (P< 0. 05). Immunofluorescence showed that the MST1 / 2 inhibitor group had less infiltration of inflammatory cells and formed a structural framework of nerve tissue, whereas the normal saline group had obvious infiltration of inflammatory cells and formed a large number of glial scars. Immunofluorescence also showed that YAP was expressed in nerve cells in the Sham operation group. Moreover, the number of YAP and GAP43-positive cells in the MST1 / 2 inhibitor group was significantly higher than that in the other two groups, and the number of mature and hypertrophic astrocyte cells in the MST1 / 2 inhibitor group was significantly lower than that in the normal saline group; double immunofluorescent staining showed that YAP and GFAP were co-expressed. Conclusions A high dose of the MST1 / 2 inhibitor decreased YAP expression, activated reactive astrocytes, reduced the inflammatory injury response, inhibited apoptosis of nerve cells, improved the microenvironment of the injured area, and promoted neurite regeneration and function recovery.