Aging impairs shear stress-dependent dilation of arteries via increased superoxide production, decreased SOD activity and decreased activation of eNOS. In the present study, we investigated whether chronic increases in shear stress, elicited by increases in blood flow, would improve vascular endothelial function of aged rats. To this end, second-order mesenteric arteries of young (6-month) and aged (24-month) male Fischer 344 rats were selectively ligated for three weeks to elevate blood flow in the first order artery (HF). An in vitro study was then conducted on first-order arteries with HF and normal blood flow (NF) to assess shear stress (1, 10, and 20 dyne/cm²)-induced release of NO into the perfusate. In HF arteries of both age groups, shear stress-induced NO production increased significantly. In 24-month-old rats, the reduced shear stress-induced NO production in NF arteries was normalized by HF to a level similar to that in NF arteries of 6-month-old rats. The increased NO production in HF arteries of 24-month-old rats was associated with increased shear stress-induced dilation, expression of eNOS protein and shear stress-induced eNOS phosphorylation. Wortmannin, a PI3 kinase inhibitor, reduced shear stress-induced eNOS phosphorylation and dilation. Superoxide production decreased significantly in HF compared to NF arteries in 24-month-old rats. The decreased superoxide production was associated with significant increases in CuZn-SOD and EC-SOD protein expressions and total SOD activity. These results suggest that stimulation by chronic high blood flow restores shear stress-induced activation of eNOS and antioxidant ability in aged arteries.