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Background: Type2 Diabetes (T2D) remains one of the most important causes of cardiovascular diseases (CVD). Menopause leads to an increase in CVD and metabolic syndrome, which indicates the role of sex steroids as a protective factor. In the present study, we surveyed the effects of 17β-estradiol (E2) alone and in combination with progesterone (P4) on cardiovascular dysfunction in T2D. Methods: Female ovariectomized (OVX) diabetic rats were divided into eight groups: Sham-Control, Diabetes (Dia), OVX + Dia, OVX + Dia + Vehicle, OVX + Dia + E2, OVX + Dia + P4, OVX + Dia + E2+P4, and OVX + Dia + E2+Vehicle. T2D was induced by a high-fat diet and streptozotocin. E2 and P4 were administrated every four days for four weeks. The heart cytokines and angiotensin II, lipid profile, insulin, water, and food intake and cardiovascular indices were measured. Results: Results showed that single treatment with E2 decreased fasting blood glucose, water, and food intake, atherogenic and cardiac risk indices, and blood pressure. Also, P4 led to a decrease in atherogenic and cardiac risk indices. TNFα and IL-6 levels were increased and IL-10 was decreased in the Dia group, while E2 alone was able to inhibit these changes. The combined use of E2 and P4 eliminated the beneficial effects of E2 on these indices. Although diabetes results in an increment of cholesterol, LDL and triglyceride, hormone therapy with E2 was associated with improved dyslipidemia. Conclusion: The use of E2 alone, and not the individual use of P4, and its combination with E2 improved cardiovascular function in OVX diabetic animals, possibly by reducing the amount of inflammatory cytokines and improving metabolic parameters.