There is an epidemic of the metabolic syndrome across the world, which is often associated with hypertension and other coronary risk factors. Insulin resistance is thought to play a key role in this condition. Several different mechanisms such as activation of renin-angiotensin system, enhancement of sympathetic nerve system, and hyperinsulinemia may underlie hypertension in metabolic syndrome. Unlike in other tissues, angiotensin II regulates renal proximal tubule transport in a biphasic manner. The molecular mechanism for the angiotensin II-mediated regulation of renal proximal transport has been recently clarified. On the other hand, insulin stimulates sodium transport in several nephron segments including proximal tubules. Recent data have shown that the sodium-retaining effect of insulin is paradoxically preserved in a mouse model of insulin resistance, which may be enhanced by sympathetic nerve activation. In this review, we will focus on the roles of abnormal renal proximal tubule sodium handling in hypertension.