Estradiol (E2) treatment initiated immediately after midlife ovariectomy (OVX) in Long Evans rats exerts positive effects on cognition. Furthermore, animals treated with short-term E2 perform as well as animals maintained on E2 for the entire study. We hypothesized that midlife E2 treatment positively impacts cognition through its protective effects on the cardiovascular system. Female retired breeders underwent OVX at 11 months of age and received an implant of E2 or vehicle (cholesterol; Ch). After 40 days, implants were replaced comprising the following groups: Ch>Ch (n=9), E2>E2 (n=7), E2>Ch (n=10). Body weight and tailcuff blood pressure were measured weekly, and at the end of the study tissue weights were obtained. In comparison to Ch>Ch, weight gain was significantly reduced only in the E2>E2 group (P<0.05). Uterine weight was significantly higher in the E2>E2 group, demonstrating the effectiveness of E2 treatment (P=0.001). Systolic blood pressure significantly increased in the Ch>Ch group (P<0.001) but not in the E2>Ch group (P>0.05) or the E2>E2 group (P>0.05). Final blood pressure was significantly lower in E2>Ch and E2>E2 groups vs. Ch>Ch (P<0.05). Our results indicate that female Long Evans rats display spontaneous hypertension in response to midlife OVX. Furthermore, both transient and sustained E2 treatment attenuated OVX-induced hypertension in this strain. Therefore, midlife hormone therapy when administered during a critical window may induce beneficial cardiovascular effects that extend well beyond the period of exposure.