Objective: Hypertension is one of the major adverse effects of tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors. However, the mechanism underlying TKIs-induced hypertension remains unclear. Here, we evaluated BP responses at different doses of apatinib, a TKI used for anti-tumor therapy, in normotensive Wistar–Kyoto rats. Furthermore, we explored the role of the RhoA/Rho kinase (ROCK) emodellin pathway in elevation of blood pressure (BP) induced by apatinib, a selective TKI approved in China for treatment of advanced or metastatic gastric cancer. A non-specific ROCK inhibitor, Y27632, was then combined with apatinib and its efficacy in alleviating apatinib-induced hypertension was evaluated. Design and method: Normotensive female Wistar–Kyoto rats were exposed to two different doses of apatinib, or apatinib combined with Y27632, or vehicle for two weeks. BP was monitored by a tail-cuff plethysmography system. The mRNA levels and protein expression in the RhoA/ROCK pathway were determined, and vascular emodelling assessed. Results: Administration of either a high or low dose of apatinib was associated with a rapid rise in BP, reaching a plateau after 12 days. Apatinib treatment mediated upregulation of RhoA and ROCK 2 in the mid-aorta, more significant in the high dose group. However, ROCK1 expression showed no statistically significant differences. Furthermore, the mRNA level of GRAF3 decreased dose-dependently. Apatinib administration was also associated with decreased levels of MLCP, and elevated endothelin-1 (ET-1) and collagen 1, which was accompanied with increased mid-aortic media. However, treatment with Y27632 attenuated the above changes. Conclusions: Results of the present study indicated that apatinib treatment increased BP and promoted vascular emodelling by activating the RhoA/ROCK emodellin pathway. However, Y27632, a non-specific ROCK inhibitor, reversed apatinib-induced increase in BP and vascular emodelling. Therefore, RhoA/ROCK activation could be the underlying mechanism of apatinib-induced hypertension, while ROCK inhibitors could be potential therapeutic drugs.