Abstract Body: Hypertension is the primary modifiable risk factor for cardiovascular disease, the number one cause of mortality worldwide. We previously demonstrated that Th17 activation and interleukin 17A (IL-17A) is integral for the full development of a hypertensive phenotype as well as the renal and vascular damage associated with hypertension. Rho-associated coiled-coil containing protein kinase 2 (ROCK2) serves as a molecular switch increasing Th17 and inhibiting regulatory T cell (Treg) differentiation of CD4+ T cells. We found that ROCK2 is upregulated in splenic CD4+ T cells in hypertensive mice, confirming the potential for influencing hypertension-associated T cell activation. We hypothesized that excessive T cell ROCK2 activation, leading to increased Th17/Treg ratios, contributes to hypertension and ultimately, end-organ damage. We first showed in vitro that KD025, an orally bioavailable ROCK2 inhibitor, inhibits Th17 proliferation and IL-17A production. We then tested the effect of ROCK2 inhibition in vivo on DOCA (deoxycorticosterone) salt-induced hypertension. DOCA-salt (uninephrectomy + 100mg DOCA pellet + 1% NaCl drinking water, n=19) was initiated in all mice allowing for hypertension to develop for 10 days, followed by treatment with the ROCK2 specific inhibitor KD025 (50mg/kg i.p. daily starting on Day 11, n=11) for the remainder of the 21-day protocol. KD025 treatment significantly attenuated cardiac hypertrophy and left ventricular fibrosis by the termination of the study. Furthermore, we observed a decrease in the Th17/Treg ratio in the heart by flow cytometry. Though KD025 is ROCK2-specific, this treatment was systemic and not limited to targeting ROCK2 in T cells. To verify that this protection is mediated through effects specifically on T cells, we obtained ROCK2 Fl/Fl mice and crossed this strain to mice expressing Cre recombinase driven by the CD4 promoter. We then subjected ROCK2^Fl/Fl CD4^Cre+ and ROCK2^Fl/Fl CD4^Cre- mice to the DOCA-salt protocol. We observed that Cre+ mice, lacking ROCK2 in T cells, exhibited an attenuation in the rise in blood pressure by Day 14 which was accompanied by reduced cardiac hypertrophy. These data indicate that the ROCK2 in T cells promotes a hypertensive state and the associated cardiac hypertrophy. Furthermore, the data show that the ROCK2-specific inhibitor KD025 may be a novel adjunct therapeutic treatment for hypertension and the associated tissue damage.